LPS-induced whole-blood cytokine production and depressive symptoms in dementia spousal caregivers: The moderating effect of childhood trauma.

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma. METHODS: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also determined lipopolysaccharide-induced whole-blood cytokine production as the primary measure of immune cell reactivity. We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) and converted z-scores of each cytokine into a composite panel. We regressed depressive symptoms on proinflammatory cytokine production, caregiver burden, and anticipatory grief, adjusting for demographic and health-related covariates. RESULTS: Whole-blood cytokine production and childhood trauma were associated with depressive symptoms. Childhood trauma moderated the relationship between whole-blood cytokine production and depressive symptoms. Whole-blood cytokine production was only associated with depressive symptoms at mean and high levels of childhood trauma, but not at low levels of childhood trauma. The main effects of burden and anticipatory grief on depressive symptoms were strongest for caregivers reporting high levels of childhood trauma. DISCUSSION: Childhood trauma has lasting impacts on psychosocial experiences later in life and has effects that may confer susceptibility to inflammation-related depression. Our findings contribute to ongoing efforts to identify risk factors for adverse mental health in dementia spousal caregivers.

Examining Links Between Distinct Affective States and Tobacco Lapse During a Cessation Attempt Among African Americans: A Cohort Study.

BACKGROUND: Affect states are posited to play a pivotal role in addiction-related processes, including tobacco lapse (i.e., smoking during a quit attempt), and distinct affective states (e.g., joy vs. happiness) may differentially influence lapse likelihood. However, few studies have examined the influence of distinct affective states on tobacco lapse. PURPOSE: This study examines the influence of 23 distinct affect states on tobacco lapse among a sample of tobacco users attempting to quit. METHODS: Participants were 220 adults who identified as African American (50% female, ages 18-74). Ecological momentary assessment was used to assess affect and lapse in real-time. Between and within-person associations testing links between distinct affect states and lapse were examined with multilevel modeling for binary outcomes. RESULTS: After adjusting for previous time's lapse and for all other positive or negative affect items, results suggested that at the between-person level, joy was associated with lower odds of lapse, and at the within-person level, attentiveness was associated with lower odds of lapse. Results also suggested that at the between-person level, guilt and nervous were associated with higher odds of lapse, and at the within-person level, shame was associated with higher odds of lapse. CONCLUSIONS: The present study uses real-time, real-world data to demonstrate the role of distinct positive and negative affects on momentary tobacco lapse. This work helps elucidate specific affective experiences that facilitate or hinder the ability to abstain from tobacco use during a quit attempt.

Perceived income inadequacy is associated with Epstein-Barr Virus latency and mental health outcomes in informal caregivers who are also employed in the healthcare industry.

Finances are a prevalent source of stress. In a sample of 799 nursing home workers measured multiple times over 18 months, we found that higher perceived income inadequacy, the perception that one's expenses exceeds one's incomes, was associated with poorer self-reported mental health indicators and Epstein-Barr Virus antibody titers (a marker of cell-mediated immune function). Perceived income inadequacy predicted outcomes over and above the role of other socioeconomic status variables (objective household income and education). Mental health variables were not related to Epstein-Barr Virus antibody titers. Additionally, we found an interaction between perceived income inadequacy and informal caregiver status on our mental health outcomes; informal caregivers with higher perceived income inadequacy had poorer mental health than non-caregivers with the same perceived income inadequacy. Our findings may add nuance to the reserve capacity model, which states that those at lower socioeconomic levels are at higher risk of adverse health outcomes partly because they have fewer resources to address demands and strain. Perceived income inadequacy may significantly predict mental and physical well-being beyond other socioeconomic status variables, especially among lower-income employees. Caregiving stress and perceived income inadequacy may have synergistic effects on mental health.

Employment and family income in psychological and immune outcomes during bereavement.

Spousal bereavement is one of the most stressful experiences in adulthood. In a sample of 183 widow(er)s, bereaved about three months prior, we examined the intersection of employment, family income, and health outcomes (proinflammatory marker production, perceived stress, and grief symptoms). Bereaved employees had higher levels of monocyte-stimulated interleukin-6, tumor necrosis factor-α, chemokine ligands 4, and perceived stress than bereaved retirees. We also found an interaction such that family income was positively associated with perceived stress and grief symptoms for employed window(er)s, but not for retirees. These findings align with the reserve capacity model, which states that people at higher levels of socioeconomic status have more psychosocial resources to address psychosocial stressors. Employment likely served as an added psychological and inflammatory burden for all bereaved workers, except those with the highest incomes.

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.

mRisk: Continuous Risk Estimation for Smoking Lapse from Noisy Sensor Data with Incomplete and Positive-Only Labels.

Passive detection of risk factors (that may influence unhealthy or adverse behaviors) via wearable and mobile sensors has created new opportunities to improve the effectiveness of behavioral interventions. A key goal is to find opportune moments for intervention by passively detecting rising risk of an imminent adverse behavior. But, it has been difficult due to substantial noise in the data collected by sensors in the natural environment and a lack of reliable label assignment of low- and high-risk states to the continuous stream of sensor data. In this paper, we propose an event-based encoding of sensor data to reduce the effect of noises and then present an approach to efficiently model the historical influence of recent and past sensor-derived contexts on the likelihood of an adverse behavior. Next, to circumvent the lack of any confirmed negative labels (i.e., time periods with no high-risk moment), and only a few positive labels (i.e., detected adverse behavior), we propose a new loss function. We use 1,012 days of sensor and self-report data collected from 92 participants in a smoking cessation field study to train deep learning models to produce a continuous risk estimate for the likelihood of an impending smoking lapse. The risk dynamics produced by the model show that risk peaks an average of 44 minutes before a lapse. Simulations on field study data show that using our model can create intervention opportunities for 85% of lapses with 5.5 interventions per day.

Immune and Epigenetic Pathways Linking Childhood Adversity and Health Across the Lifespan.

Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.

Inflammation and future depressive symptoms among recently bereaved spouses.

Major depressive disorder (MDD) is an important contributor to the total disease burden because of its high comorbidity with chronic illnesses. Many people with high levels of depressive symptoms exhibit elevated systemic inflammation, but inflammation is not a necessary determinant of depression onset. Among those who recently experienced the death of a spouse, we investigated whether (a) inflammation assessed early in bereavement predicted future depressive symptoms and whether (b) inflammation predicted change in depressive symptoms from baseline to follow-up. Ninety-nine spousally bereaved individuals (M=68.61, SD=10.70) from a larger study were evaluated at baseline (3 months post-death) and follow-up (6 months post-death). Subjects received a venous blood draw and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Stimulated T-cell derived cytokines (IL-6, TNF-α, and IFN-γ) were assessed individually and as a pro-inflammatory composite index. After controlling for confounding factors (i.e., age, sex, body mass index, race, ethnicity, anti-inflammatory medication, days since spousal death, smoking status, comorbidities), individuals with higher levels of IL-6, TNF-α, and IFN-γ at baseline exhibited more depressive symptoms (composite index, p = .05) and an increased probability of experiencing clinical levels of depression (CES-D score ≥16) (composite index, p = .04). Inflammatory levels were not predictive of change in depressive symptoms or in clinical depression status from baseline to follow-up. Among individuals who did not experience clinical levels of depression at baseline, baseline inflammatory levels predicted clinical levels of depression 3 months later (p = .03). This study provides support for an inflammatory mechanism underlying depression following bereavement. It suggests that one's inflammatory profile following a significant social stressor in older adulthood can be prognostic of depression risk months later. These findings add to our understanding of the physiological and mental health risks experienced by the bereaved population and provide insight into identifying vulnerable widow(er)s at risk for maladaptive grief coping.

Associations of meaning of illness with psychosocial, clinical, and immunological characteristics in patients with Leptomeningeal metastasis.

Background: Leptomeningeal metastasis (LM) creates symptoms related to both the disease within the nervous system and treatment toxicities. Biologic processes, such as inflammation and behavioral processes, such as the meaning ascribed to illness (Meaning of Illness: MoI), can impact physical and psychosocial symptoms. The aim of this study was to understand the relationships among MoI, physical and psychosocial symptoms, and inflammation in patients with LM. Methods: Thirty enrolled participants completed the MD Anderson Symptom Inventory-Brain Tumor with spine experimental symptoms added. Meaning of illness, quality of life (QoL), and depression were captured by validated instruments. Interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum and cerebrospinal fluid (CSF) were measured by ELISA. Correlations were performed to assess relationships among the variables. Results: Participants were primarily white (73%), female (63%). Median age was 54 years (34-83). Breast (50%) and lung (20%) were most common diagnosis. Higher MoI scores were associated with better QoL (p < .01) and fewer depressive symptoms (p < .01). All CSF samples contained IL-6 and all but one sample had elevated IL-6. Higher levels of IL-6 in the CSF were associated with greater symptom burden (p < .01) and interference of symptoms in daily life (p = .02) but not MoI. Conclusions: MoI was associated with QoL and depression. High levels of IL-6 in the CSF were associated with more severe symptoms. This study provides the groundwork for future research, including interventional studies to improve QoL in patients with LM.

SmokingOpp: Detecting the Smoking 'Opportunity' Context Using Mobile Sensors.

Context plays a key role in impulsive adverse behaviors such as fights, suicide attempts, binge-drinking, and smoking lapse. Several contexts dissuade such behaviors, but some may trigger adverse impulsive behaviors. We define these latter contexts as 'opportunity' contexts, as their passive detection from sensors can be used to deliver context-sensitive interventions. In this paper, we define the general concept of 'opportunity' contexts and apply it to the case of smoking cessation. We operationalize the smoking 'opportunity' context, using self-reported smoking allowance and cigarette availability. We show its clinical utility by establishing its association with smoking occurrences using Granger causality. Next, we mine several informative features from GPS traces, including the novel location context of smoking spots, to develop the SmokingOpp model for automatically detecting the smoking 'opportunity' context. Finally, we train and evaluate the SmokingOpp model using 15 million GPS points and 3,432 self-reports from 90 newly abstinent smokers in a smoking cessation study.

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.

Emotion Regulation and Immune Functioning During Grief: Testing the Role of Expressive Suppression and Cognitive Reappraisal in Inflammation Among Recently Bereaved Spouses.

OBJECTIVE: Losing a spouse is a distressing life event that can negatively affect both mental and physical health. Stress-induced health consequences often include increased risk of cardiovascular disease and altered immune system functioning marked by increased inflammation. Here, we sought to identify individual difference factors that covary with problematic inflammatory outcomes. METHOD: We measured recently bereaved spouses' (n = 99) propensity to use emotion regulation strategies and peripheral inflammation, as measured by levels of proinflammatory cytokines after ex vivo stimulation of peripheral leukocytes with T-cell agonists. Specifically, we measured participants' use of cognitive reappraisal, an adaptive emotion regulation strategy in many contexts, and expressive suppression, a less adaptive emotion regulation strategy that involves actively inhibiting emotions after already experiencing them. RESULTS: Bereaved spouses who self-reported frequently using expressive suppression as an emotion regulation strategy tended to have a more pronounced inflammatory response, as indexed by higher levels of a composite cytokine index consisting of interleukin (IL) 17A, IL-2, IL-6, tumor necrosis factor α, and interferon-γ (b = 0.042), as well as tumor necrosis factor α (b = 0.083) and interferon-γ (b = 0.098) when analyzed individually. Notably, these associations were observed in both unadjusted and adjusted models, with the latter including known covariates of inflammation and other potential confounding variables. CONCLUSIONS: These findings suggest that bereaved spouses' use of emotion regulation strategies is associated with altered immune functioning, and such a link may be an important biological pathway by which interventions targeting affect may improve immune system-related health outcomes.

Feasibility and acceptability of a faith-based mind-body intervention among African American adults.

Physical activity reduces cancer risk, yet African American adults remain insufficiently active, contributing to cancer health disparities. Harmony & Health (HH) was developed as a culturally adapted mind-body intervention to promote physical activity, psychosocial well-being, and quality of life among a church-based sample of overweight/obese, insufficiently active African American adults. Men and women were recruited to the study through an existing church partnership. Eligible participants (N = 50) were randomized to a movement-based mind-body intervention (n = 26) or waitlist control (n = 24). Participants in the intervention attended 16 mind-body sessions over 8 weeks and completed a physical assessment, questionnaires on moderate-to-vigorous physical activity (MVPA) and psychosocial factors, and accelerometry at baseline (T1), post-intervention (T2), and 6 week follow-up (T3). Eighty percent of participants (94% women, M age = 49.7 ± 9.4 years, M body mass index = 32.8 ± 5.2 kg/m2) completed the study, and 61.5% of intervention participants attended ≥10 mind-body sessions. Participants self-reported doing 78.8 ± 102.9 (median = 40.7, range: 0-470.7) min/day of MVPA and did 27.1 ± 20.7 (median = 22.0, range: 0-100.5) min/day of accelerometer-measured MVPA at baseline. Trends suggest that mind-body participants self-reported greater improvements in physical activity and psychosocial well-being from baseline to post-intervention than waitlist control participants. HH is feasible and acceptable among African American adults. Trends suggest that the mind-body intervention led to improvements in physical activity and psychosocial outcomes. This study extends the literature on the use of mind-body practices to promote physical and psychological health and reduce cancer disparities in African American adults.

Church Attendance and CMV Herpes Virus Latency Among Bereaved and Non-Bereaved Adults.

OBJECTIVE: There is widespread literature linking church attendance to physical health. However, little is known about the association of church attendance and the immune system, particularly during difficult life transitions. This study investigated the association between church attendance and CMV herpes-virus latency by assessing Cytomegalovirus (CMV) IgG antibody titers among bereaved and non-bereaved individuals. METHODS: Participants included 44 bereaved individuals and 44 controls with a mean age of 68 (SD=12.84). CMV herpes-virus latency was measured using CMV IgG antibody titers. Church attendance was measured using three items from the Community Healthy Activities Model Program for Seniors (CHAMPS) Questionnaire. RESULTS: After adjusting for participant's age, gender, education, minority status, weekly alcohol consumption, smoking, depression, body mass index (BMI) and comorbidities, church attendance was associated with lower CMV IgG antibody titers among bereaved and control participants. Further, there was a significant moderating effect of church attendance in the association between bereavement status and CMV IgG antibody titers, so that bereaved individuals attending church were found to have less herpes-virus reactivation (lower CMV IgG antibody titers) when compared to their bereaved counterparts that do not attend church. CONCLUSION: This study demonstrated that church attendance is associated with less herpes-virus reactivation as indexed by lower levels of CMV IgG antibody titers, particularly among the bereaved. Future studies should focus on further understanding the pathways by which church attendance impacts CMV herpes-virus latency during stressful life events, such as bereavement.

Sex differences in executive functioning and latent herpesvirus reactivation among bereaved and nonbereaved individuals.

The death of a spouse is a highly stressful event. Better executive functioning has been shown to benefit men to a greater degree than women during stress. We evaluated potential sex differences in stress and immune dysregulation among control and bereaved participants who completed a self-report measure of perceived stress, neuropsychological measures of inhibition and updating/monitoring of information in working memory, and a blood draw to measure Epstein-Barr virus (EBV) antibody titres. Moderation analyses were conducted to test the hypothesis that better inhibition would be associated with less stress and immune dysregulation among male bereaved participants compared with female bereaved participants. Bereaved females demonstrated greater EBV antibody titres than bereaved males. Male bereaved participants benefited from better inhibition, as evidenced by fewer EBV antibody titres, whereas bereaved female participants did not. In the control group, males with high inhibition reported lower stress than males with low inhibition. Present study results are an important step towards identifying those at greatest risk of stress and poor health.

Psychological and Biological Pathways Linking Perceived Neighborhood Characteristics and Body Mass Index.

BACKGROUND: Perceived neighborhood characteristics are linked to obesity, however, the mechanisms linking these two factors remain unknown. PURPOSE: This study aimed to examine associations between perceived neighborhood characteristics and body mass index (BMI), establish whether indirect pathways through psychological distress and inflammation are important, and determine whether these associations vary by race/ethnicity. METHODS: Participants were 1,112 adults enrolled in the Texas City Stress and Health Study. Perceived neighborhood characteristics were measured using the Perceived Neighborhood Scale. Psychological distress was measured with the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale and mental health subscale of the Short Form Health Survey-36. Markers of inflammation included C-reactive protein, interleukin-6, and tumor necrosis factor receptor-1. Associations were examined with Structural Equation Modeling. RESULTS: A model linking neighborhood characteristics with BMI through direct and indirect (i.e., psychological distress and inflammation) paths demonstrated good fit with the data. Less favorable perceived neighborhood characteristics were associated with greater psychological distress (B = -0.87, ß = -0.31, p < .001) and inflammation (B = -0.02, ß = -0.10, p = .035). Psychological distress and inflammation were also significantly associated with BMI (Bdistress = 0.06, ß = 0.08, p = .006; Binflammation = 4.65, ß = 0.41, p < .001). Indirect paths from neighborhood characteristics to BMI via psychological distress (B = -0.05, ß = -0.03, p = .004) and inflammation (B = -0.08, ß = -0.04, p = .045) were significant. In multiple group analysis, a model with parameters constrained equal across race/ethnicity showed adequate fit suggesting associations were comparable across groups. CONCLUSION: Our study extends the literature by demonstrating the importance of neighborhood perceptions as correlates of BMI across race/ethnicity, and highlights the role of psychological and physiological pathways.

Grief, depressive symptoms, and inflammation in the spousally bereaved.

Grief is conceptualized by strong negative emotions, which include longing, sadness, and preoccupations with thoughts, recollections, and images of the spouse. In the initial months after the loss of a spouse, those who are widowed are at risk for cardiovascular problems and premature mortality. In the general population, depression is characterized by chronic low-grade inflammation, a key predictor of cardiovascular problems, morbidity, and mortality. Although depression and grief share similarities, they are distinct constructs. We aimed to identify if grief was related to inflammation among those who had a spouse recently die. We also sought to determine if those who are widowed and already experience elevated levels of depressive symptoms compared with the general population had higher levels of inflammation compared with those who are widowed who report fewer depressive symptoms. Ninety-nine recently bereaved individuals (M = 84.74 days since passing, SD = 18.17) completed a blood draw and psychological assessments. Proinflammatory T cell-derived cytokines were assessed, which included interferon gamma (IFN-γ), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL17-A, and IL-2. Bereaved individuals with a higher grief severity (using an established cut-score) had higher levels of the proinflammatory cytokines IFN-γ, IL-6, and TNF-α than those with less grief severity. Those who experienced higher levels of depression exhibited elevated levels of proinflammatory cytokines compared with those who had lower levels of depression (using a continuous measure of depressive symptoms, as well as an established cut score). This is the first study to demonstrate that inflammatory markers can distinguish those who are widowed based on grief severity such that those who are higher on grief severity have higher levels of inflammation compared with those who are lower on grief severity. These findings also add to the broader literature on depression and inflammation by showing that even in a population with high levels of depressive symptoms, there is a positive relationship between depression and inflammation.

Impaired mental health and low-grade inflammation among fatigued bereaved individuals.

BACKGROUND: Fatigue is a common symptom in stressed individuals. Bereavement is a major life event that has been associated with impaired mental health. Little research has investigated the prevalence of fatigue and its inflammatory correlates in bereaved individuals. OBJECTIVES: To assess fatigue prevalence and its relationship with mental health outcomes and markers of inflammation, as indexed by C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in bereaved individuals. METHODS: Seventy-eight-bereaved adults were examined for fatigue (SF-36 energy/vitality scale), perceived stress (PSS), depression (CES-D), sleep quality (PSQI), pain (SF-36 pain scale), and general health (SF-36 general), and their serum levels of CRP, IL-6 and TNF-α were measured. Group differences between fatigued versus non-fatigued individuals were estimated using analysis of covariance (ANCOVA), with adjustment for body mass index (BMI). RESULTS: Fatigued bereaved individuals (33%; SF-36 energy/vitality score 0-45) had significantly higher CRP levels (p < .05) as compared to non-fatigued bereaved individuals and reported higher levels of pain (p < .001), greater stress (p < .001), depression (p < .001), and sleeping problems (p < .001), as well as poorer social functioning (p < .001) and general health (p < .001) than those in the non-fatigued group. No group differences were found for IL-6 and TNF-α. CONCLUSIONS: Fatigued bereaved individuals showed elevated systemic inflammation as measured by CRP in comparison to non-fatigued bereaved individuals. They were also more likely to report mental health problems that co-occur with fatigue in the context of immune activation. Continued research is needed to help clarify the involvement of inflammatory markers in the development of fatigue in a larger sample of bereaved adults.

Marital distress, depression, and a leaky gut: Translocation of bacterial endotoxin as a pathway to inflammation.

BACKGROUND: Marital distress and depression work in tandem to escalate risks for inflammation-related disorders. Translocation of bacterial endotoxin (lipopolysaccharide, LPS) from the gut microbiota to blood circulation stimulates systemic inflammatory responses. METHODS: To investigate increased gut permeability (a "leaky gut") as one potential mechanistic pathway from marital distress and depression to heightened inflammation, this secondary analysis of a double-blind, randomized crossover study examined serial assessments of two endotoxin biomarkers, LPS-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) during two separate 9.5 h visits. The 43 (N = 86) healthy married couples, ages 24-61 (mean = 38.22), discussed a marital disagreement during both visits; behavioral coding of these interactions provided data on hostile marital behaviors, a hallmark of marital distress. The Structured Diagnostic Interview for DSM-IV assessed participants' mood disorder history. RESULTS: Participants with more hostile marital interactions had higher LBP than those who were less hostile. Additionally, the combination of more hostile marital interactions with a mood disorder history was associated with higher LBP/sCD14 ratios. Higher LBP and LBP/sCD14 were associated with greater CRP production; for example, only 21% of low LBP participants (lowest quartile) had average CRP across the day > 3, compared to 79% of those in the highest quartile. Higher sCD14 was associated with higher IL-6. CONCLUSIONS: These bacterial LPS translocation data illustrate how a distressed marriage and a mood disorder history can promote a proinflammatory milieu through increased gut permeability, thus fueling inflammation-related disorders.