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.

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults.

OBJECTIVE: Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. METHODS: We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1ß, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. RESULTS: Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition ( B = -2.36, standard error = 1.06, p = .028) and cognitive flexibility ( B = -2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. CONCLUSIONS: These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

Ex vivo LPS-stimulated cytokine production is associated with cortisol curves in response to acute psychosocial stress.

BACKGROUND: Empirical and theoretical evidence suggest that because of the co-evolution of the endocrine and immune response systems, different types of stressors may lead to similar levels of physiological activation. The present analyses examined associations between two physiological stress responses: the cortisol response to an acute laboratory stressor and ex vivo lipopolysaccharide (LPS) stimulated inflammatory cytokine production. METHODS: Healthy middle-aged adults (N = 65) completed testing at two appointments, two weeks apart. Blood was collected at each appointment to measure circulating inflammatory cytokine levels and stimulated inflammatory cytokine production after 4 and 24 hours of incubation with LPS. A cumulative standardized composite measure of inflammation was calculated using the cytokines interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and interferon-γ (IFN-γ). At visit two, after the blood draw, participants completed the Trier Social Stress Test (TSST); saliva samples were collected before and after to generate cortisol response curves (area under the curve with respect to ground [AUCG] and increase/decrease [AUCI]). RESULTS: AUCG was significantly associated with stimulated cytokine production at visit 2 after both 4 hours (B = 6.89; p = 0.007) and 24 hours (B = 7.50; p = 0.005) of incubation, controlling for age, sex, and BMI. AUCI was also significantly associated with stimulated cytokine production at visit 2 after 4 hours (B = 6.28; p = 0.004) and 24 hours (B = 6.16; p = 0.007) of incubation, controlling for age, sex, and BMI. Stimulated inflammatory cytokine production was strongly correlated across the two visits (2 weeks apart) after 4 hours of incubation (r = 0.80, p < 0.001) and after 24 hours (r = 0.80, p < 0.001). Within each visit, stimulated cytokine production after 4 hours was significantly correlated with stimulated inflammation at 24 hours (r = 0.93-0.94, p < 0.05) CONCLUSIONS: These results suggest that LPS-stimulated inflammatory cytokine production and the cortisol response to the TSST contain comparable information about acute human physiological stress responses. Moreover, measurement of stimulated cytokines was highly stable across a two-week time period whether measured after 4 or 24 hours of incubation with LPS.

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.

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.

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.

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.

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.

Inhibition is associated with metabolic syndrome and depression through inflammation.

Inhibition is the ability to stop one's self from responding, or paying attention, to tempting/distracting stimuli or thoughts. Those with poor inhibition are at greater risk of depression and a variety of diseases of older adulthood than those with better inhibition. Inflammation may be a mechanism underlying these links. A total of 840 participants from the Midlife in the United States study completed a neuropsychological measure of inhibition, a self-report measure of depressive symptoms, and a blood draw. Results indicated that poor inhibition was associated with high interleukin-6 (IL-6). Inhibition was indirectly associated with metabolic syndrome incidence and depressive symptoms through IL-6. Findings suggest that IL-6 may be a mechanism linking inhibition with metabolic syndrome and depression.

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.

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.

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.

Executive functioning and diabetes: The role of anxious arousal and inflammation.

Individuals who perform poorly on measures of the executive function of inhibition have higher anxious arousal in comparison to those with better performance. High anxious arousal is associated with a pro-inflammatory response. Chronically high anxious arousal and inflammation increase one's risk of developing type 2 diabetes. We sought to evaluate anxious arousal and inflammation as underlying mechanisms linking inhibition with diabetes incidence. Participants (N=835) completed measures of cognitive abilities, a self-report measure of anxious arousal, and donated blood to assess interleukin-6 (IL-6) and glycated hemoglobin (HbA1c). Individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the serial pathway from high anxious arousal to IL-6. Findings remained when entering other indicators of cognitive abilities as covariates, suggesting that inhibition is a unique cognitive ability associated with diabetes incidence. On the basis of our results, we propose several avenues to explore for improved prevention and treatment efforts for type 2 diabetes.