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ABSTRACT: The "geroscience hypothesis" posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. Although geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome-the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity.
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Envelhecimento , Humanos , Envelhecimento/fisiologia , Gerociência , Determinantes Sociais da Saúde , Expossoma , Estresse Psicológico , Meio SocialRESUMO
OBJECTIVE: Psychosocial stress is transduced into disease risk through energy-dependent release of hormones from the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes. The levels of glucocorticoid and adrenergic hormones, together with the sensitivity of tissues to their signaling, define stress responses. To understand existing pathways responsible for the psychobiological transduction of stressful experiences, we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor (AR) expression. METHODS: We systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and ß-ARs (AR-α1B, AR-α2B AR-ß2, and AR-ß3), across 55 different organs using the Human Protein Atlas and Human Proteome Map datasets. Given that mitochondria produce the energy required to respond to stress, we leveraged the Human Protein Atlas and MitoCarta3.0 data to examine the link between stress hormone receptor density and mitochondrial gene expression. Finally, we tested the functional interplay between GR activation and AR expression in human fibroblast cells. RESULTS: The GR was expressed ubiquitously across all investigated organ systems, whereas AR subtypes showed lower and more localized expression patterns. Receptor co-regulation, meaning the correlated gene expression of multiple stress hormone receptors, was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In cultured human fibroblasts, activating the GR selectively increased AR-ß2 and AR-α1B expression. Consistent with the known energetic cost of stress responses, GR and AR expressions were positively associated with the expression of specific mitochondrial pathways. CONCLUSIONS: Our results provide a cartography of GR and AR expression across the human body. Because stress-induced GR and AR signaling triggers energetically expensive cellular pathways involving energy-transforming mitochondria, the tissue-specific expression and co-expression patterns of hormone receptor subtypes may in part determine the resilience or vulnerability of different organ systems.
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Glucocorticoides , Receptores Adrenérgicos , Humanos , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo , Transdução de Sinais , Receptores de Glucocorticoides/metabolismoRESUMO
Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling. Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017). Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.
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Antineoplásicos Hormonais , Neoplasias da Mama , Cognição , Terapia por Exercício , Exercício Físico , Pós-Menopausa , Humanos , Feminino , Neoplasias da Mama/psicologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Pós-Menopausa/psicologia , Idoso , Terapia por Exercício/métodos , Antineoplásicos Hormonais/uso terapêutico , Memória , Resultado do TratamentoRESUMO
Historical structural racism in the built environment contributes to health inequities, yet to date, research has almost exclusively focused on racist policy of redlining. We expand upon this conceptualization of historical structural racism by examining the potential associations of probable blockbusting, urban renewal, and proximity to displacement from freeway construction, along with redlining, to multiple contemporary health measures. Analyses linked historical structural racism, measured continuously at the census-tract level using archival data sources, to present-day residents' physical health measures drawn from publicly accessible records for Allegheny County, Pennsylvania. Outcome measures included average life expectancy and the percentage of residents reporting hypertension, stroke, coronary heart disease, smoking, insufficient sleep, sedentary behavior, and no health insurance coverage. Multiple regression analyses were conducted to examine separate and additive associations between structural racism and physical health measures. Redlining, probable blockbusting, and urban renewal were associated with shorter life expectancy and a higher prevalence of cardiovascular conditions, risky health behaviors, and residents lacking health insurance coverage. Probable blockbusting and urban renewal had the most consistent correlations with all 8 health measures, while freeway displacement was not reliably associated with health. Additive models explained a greater proportion of variance in health than any individual structural racism measure alone. Moreover, probable blockbusting and urban renewal accounted for relatively more variance in health compared to redlining, suggesting that research should consider these other measures in addition to redlining. These preliminary correlational findings underscore the importance of considering multiple aspects of historical structural racism in relation to current health inequities and serve as a starting point for additional research.
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Racismo , Humanos , Pennsylvania/epidemiologia , Ambiente Construído , Feminino , Disparidades nos Níveis de Saúde , Masculino , Nível de Saúde , Expectativa de Vida , Pessoa de Meia-Idade , AdultoRESUMO
PURPOSE: The war metaphor is one strategy used frequently in breast cancer to inspire individuals in a "fight" against cancer and assist patients in navigating their illness experience. Despite prominent use, the emotional impact of this language has not been examined in the context of meaning making among women with metastatic breast cancer (MBC). METHODS: This study involved a semi-structured interview considering the war metaphor's impact on women's illness experience with MBC. Participants (n = 22) had been diagnosed with MBC for at least 6 months or following 1 disease progression and were undergoing treatment at an NCI-designated cancer center in Western Pennsylvania at the time of interview. Each participant underwent an individual interview exploring the war metaphor's impact on illness experience. Qualitative thematic analysis was performed to assess feelings about the war metaphor and emotional response to the lived experience of cancer. RESULTS: Two themes were identified surrounding metaphor use and participants' experiences with meaning making in cancer. First, women with MBC perceive the diagnosis as an "unfair fight" due to its incurable nature. Second, patients use alternative language of "living life" and communicate resistance to being defined by their cancer diagnosis. CONCLUSION: War metaphors are one collection of terminology people use to understand their diagnosis. However, their use may apply pressure to prioritize positivity in the face of diagnosis and treatment, in a unique clinical context where this may not be adaptive. These findings affirm a need to consider patients' lived experiences to best facilitate psychological adjustment to illness.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Metáfora , Progressão da Doença , Emoções , IdiomaRESUMO
OBJECTIVE: Residing in communities characterized by socioeconomic disadvantage confers risk of cardiometabolic diseases. Residing in disadvantaged communities may also confer the risk of neurodegenerative brain changes via cardiometabolic pathways. This study tested whether features of communities-apart from conventional socioeconomic characteristics-relate not only to cardiometabolic risk but also to relative tissue reductions in the cerebral cortex and hippocampus. METHODS: Participants were 699 adults aged 30 to 54 years (340 women; 22.5% non-White) whose addresses were geocoded to compute community indicators of socioeconomic disadvantage, as well as air and toxic chemical pollutant exposures, homicide rates, concentration of employment opportunities, land use (green space), and availability of supermarkets and local resources. Participants also underwent assessments of cortical and hippocampal volumes and cardiometabolic risk factors (adiposity, blood pressure, fasting glucose, and lipids). RESULTS: Multilevel structural equation modeling demonstrated that cardiometabolic risk was associated with community disadvantage ( ß = 0.10, 95% confidence interval [CI] = 0.01 to 0.18), as well as chemical pollution ( ß = 0.11, 95% CI = 0.02 to 0.19), homicide rates ( ß = 0.10, 95% CI = 0.01 to 0.18), employment opportunities ( ß = -0.16, 95% CI = -0.27 to -0.04), and green space ( ß = -0.12, 95% CI = -0.20 to -0.04). Moreover, cardiometabolic risk indirectly mediated the associations of several of these community features and brain tissue volumes. Some associations were nonlinear, and none were explained by participants' individual-level socioeconomic characteristics. CONCLUSIONS: Features of communities other than conventional indicators of socioeconomic disadvantage may represent nonredundant correlates of cardiometabolic risk and brain tissue morphology in midlife.
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Doenças Cardiovasculares , Humanos , Adulto , Feminino , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Parques Recreativos , Fatores de Risco de Doenças Cardíacas , Fatores Socioeconômicos , Características da Vizinhança , Crime , Características de ResidênciaRESUMO
OBJECTIVE: Aging is associated with increased pro-inflammatory gene expression and systemic inflammation, and psychosocial stress may accelerate these changes. Mindfulness interventions show promise for reducing psychosocial stress and extending healthspan. Inflammatory pathways may play a role. In a sample of lonely older adults, we tested whether mindfulness training reduces proinflammatory gene expression and protein markers of systemic inflammation. METHODS: Lonely older adults (65-85 years; N = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or matched Health Enhancement Program (HEP). Blood was drawn pre- and post-intervention and at 3-month follow-up. In peripheral blood mononuclear cells (PBMCs), RNA profiling was used to assess transcriptional regulation by pro-inflammatory NF-kB as well as ß-adrenergic CREB, antiviral IRF, and glucocorticoid receptor (GR) transcription factors. Plasma was assayed for proinflammatory markers IL-6 and CRP. Analyses tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects. RESULTS: MBSR reduced NF-kB (d = .17, p = .028) but did not alter CREB (d = .10, p = .20), IRF (d = .13, p = .086), or GR activity (d = .14, p = .063) relative to HEP over time. Contrary to predictions, there were no time × condition effects of MBSR compared to HEP on reducing circulating IL-6 or CRP. CONCLUSIONS: In lonely older adults, MBSR reduced cellular pro-inflammatory gene regulation in ways that would predict reduced disease risk. However, no similar effect was observed for circulating protein markers of inflammation. These results provide specificity about how mindfulness interventions may impact distinct inflammatory markers among aging adults in ways that may have important implications for healthspan. TRIAL REGISTRATION: Clinical Trials identifier NCT02888600.
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Peripheral immune markers are widely used to predict risk for inflammatory disease. However, whether single assessments of inflammatory biomarkers represent stable individual differences remains unclear. We reviewed 50 studies (N = 48,674; 57 % male; mean age 54 (range 13-79) years) that assessed markers of inflammation on >1 occasion, with time between measures ranging from 24 h to 7+ years. Separate random effects meta-analyses were conducted for each inflammatory marker and time interval. Markers that had broad coverage across most time intervals included C-reactive protein (CRP; k = 37), interleukin (IL)-6 (k = 22), TNF-α (k = 10), and fibrinogen (Fg; k = 9). For CRP, IL-6, and TNF-α, stability estimates generally decreased with time, with strong to moderate stability over intervals <6 months (r's = 0.80-0.61), modest to moderate stability over 6 months - 3 years (r's = 0.60-0.51), and low stability for >3 years (r's = 0.39-0.30). Estimates were less reliable for Fg for time intervals ≤ 3 years although they generally followed the same pattern; more reliable findings suggested greater stability for Fg than other markers for intervals >3 years (r = 0.53). These findings suggest that single measures of inflammatory biomarkers may be an adequate index of stable individual differences in the short term (<6 months), with repeated measures of inflammatory biomarkers recommended over intervals ≥ 6 months to 3 years, and absolutely necessary over intervals >3 years to reliably identify stable individual differences in health risk. These findings are consistent with stability estimates and clinical recommendations for repeated measurement of other cardiovascular measures of risk (e.g., blood lipids, blood pressure).
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Projetos de Pesquisa , Fator de Necrose Tumoral alfa , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , BiomarcadoresRESUMO
BACKGROUND: Subjective social status (SSS) refers to a person's perception of their social rank relative to others and is cross-sectionally linked to systemic inflammation independently of objective socioeconomic status. PURPOSE: We test the extent to which SSS relates to multiyear changes in inflammation, or if associations differ by race or sex. METHODS: Healthy adults (N = 331; 30-51 years) completed a baseline visit and 278 participants returned for a second visit 2.85 years later. At both visits, participants underwent a fasting blood draw and completed community (SSSC) and US (SSSUS) versions of the MacArthur Scale. Multiple linear regression analyses examined change in interleukin-6 (IL-6) and C-reactive protein (CRP) predicted by each type of SSS, adjusting for time between visits, sex, race, age, body mass index, smoking, baseline inflammation, and objective socioeconomic status. Additional analyses further adjusted for hopelessness and depressive symptoms. Interactions examined moderations by sex and race. RESULTS: Lower SSSC was longitudinally associated with greater IL-6 independently of all covariates, including education and income (ß = -0.06), hopelessness (ß = -0.06), and depressive symptoms (ß = -0.06). Lower SSSUS was longitudinally associated with greater IL-6 independently of demographic covariates including education and income (ß = -0.06), but was slightly attenuated after adjusting for hopelessness (ß = -0.06) and depressive symptoms (ß = -0.06). There were no associations for CRP or moderation by race or sex. CONCLUSIONS: Lower SSS may be associated with greater circulating markers of inflammation over time as suggested by increases in IL-6.
Subjective social status (SSS) refers to how people perceive their social rank compared with others and has been linked to meaningful differences in physical health. Increases in inflammation may contribute to associations between lower SSS and poorer physical health. In a sample of healthy adults, we examined whether SSS was associated with prospective, multiyear changes in markers of systemic inflammation and if this differed by sex or race. We found that adults who perceived their social status as lower than peers in their community exhibited an accelerated increase in interleukin-6, a marker of systemic inflammation, over a 3-year period. When participants were asked to compare themselves to people in the broader USA, the pattern was similar but less robust. Results were independent of individual differences in sociodemographic characteristics including family-adjusted income and education. Findings did not differ by sex or race and were not explained by differences in adiposity and symptoms of depression and hopelessness. Effects for C-reactive protein, a second marker of inflammation, were generally nonsignificant. Although preliminary, findings suggest an immune pathway by which perceived social status may relate to chronic diseases of aging.
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Interleucina-6 , Status Social , Adulto , Humanos , Classe Social , Inflamação , Proteína C-ReativaRESUMO
BACKGROUND: Childhood socioeconomic disadvantage is associated with increased risk for chronic inflammation and cardiometabolic disease at midlife. PURPOSE: As it is presently unknown whether inflammation mediates the relationship between childhood socioeconomic status (SES) and adulthood cardiometabolic risk, we investigated associations between retrospectively reported childhood SES, circulating levels of inflammatory markers, and a latent construct of cardiometabolic risk in midlife adults. METHODS: Participants were 1,359 healthy adults aged 30-54 (Adult Health and Behavior I&II; 52% women, 17% Black) who retrospectively reported childhood SES (parental education, occupational grade). Measures included plasma interleukin (IL)-6, C-reactive protein (CRP), and cardiometabolic risk factors. Structural equation modeling was conducted, with cardiometabolic risk modeled as a second-order latent variable with adiposity, blood lipids, glucose control, and blood pressure as first-order components. RESULTS: Lower childhood SES was associated with greater risk for cardiometabolic disease at midlife (ß = -0.08, CI[-0.04, -0.01], p = .01) in models adjusted for demographics, but this association was attenuated in models that adjusted for adulthood SES and health behaviors. In fully-adjusted models, the relationship between lower childhood SES and adult cardiometabolic risk was partially explained by higher circulating levels of CRP (ß = -0.05, CI[-0.02, -0.01], p = .001), but not by IL-6. In an exploratory model, lower adulthood SES was also found to independently contribute to the association between childhood SES and adult cardiometabolic risk (ß = -0.02, CI[-0.01, -0.001], p = .02). CONCLUSIONS: The current study provides initial evidence that systemic inflammation may contribute to childhood socioeconomic disparities in cardiometabolic risk in midlife. Future work would benefit from prospective investigation of these relationships.
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Doenças Cardiovasculares , Disparidades Socioeconômicas em Saúde , Adulto , Criança , Feminino , Humanos , Masculino , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/epidemiologia , Inflamação , Interleucina-6 , Estudos Prospectivos , Estudos Retrospectivos , Classe Social , Fatores Socioeconômicos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Several personality traits increase the risk for atherosclerotic cardiovascular disease. Because many of these traits are correlated, their associations with disease risk could reflect shared variance, rather than unique contributions of each trait. We examined a higher-order personality trait of Stability as related to preclinical atherosclerosis and tested whether any such relationship might be explained by correlated variation in cardiometabolic risk factors. METHOD: Among 798 community volunteers, lower-order traits of Neuroticism, Agreeableness, and Conscientiousness were modeled as latent variables (from self- and informant ratings) and used to estimate the second-order factor, Stability. Cardiometabolic risk was similarly modeled from indicators of glycemic control, blood pressure, adiposity, and lipids. Carotid artery atherosclerosis was measured as intima-media thickness (IMT) by duplex ultrasonography. RESULT: A structural equation model incorporating direct and indirect effects showed lower Stability associated with greater IMT, and this relationship was accounted for by the indirect pathway via cardiometabolic risk. Secondary analyses showed that: (1) Neuroticism, Agreeableness, and Conscientiousness were unrelated to IMT independent of Stability; and (2) Stability predicted variation in IMT when estimated from informant-, but not self-rated, traits. CONCLUSION: Personality traits may associate with atherosclerotic burden through their shared, rather than unique, variance, as reflected in Stability.
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Aterosclerose , Espessura Intima-Media Carotídea , Humanos , Personalidade/fisiologia , Artérias Carótidas/diagnóstico por imagem , Neuroticismo , Fatores de RiscoRESUMO
OBJECTIVE: Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time. METHODS: Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child's cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3). RESULTS: Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 â T3; B = -0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 â T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time. CONCLUSIONS: This study provides a first indication that chronic stress-related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor.
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Mães , Neoplasias , Criança , Feminino , Seguimentos , Humanos , Inflamação , Neoplasias/complicações , Isolamento Social , Estresse PsicológicoRESUMO
Loneliness is a potent psychosocial stressor that predicts poor health and mortality among older adults, possibly in part by accelerating age-related declines in immunocompetence. Mindfulness interventions have shown promise for reducing loneliness and improving markers of physical health. In a sample of lonely older adults, this two-arm parallel trial tested whether mindfulness training enhances stimulated interleukin-6 (IL-6) production, a measure of innate immune responsivity. Lonely older adults (65-85 years; N = 190) were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR) or control Health Enhancement Program (HEP) intervention. Lipopolysaccharide (LPS)-stimulated production of IL-6 was measured in vitro by blinded outcome assessors at pre-intervention, post-intervention, and 3-month follow-up. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR vs. HEP) effects. As predicted, a significant time × condition effect on stimulated IL-6 production was observed across pre, post, and follow-up timepoints. Significant MBSR vs. HEP differences emerged from pre- to post-intervention (p =.009, d = 0.38) and from pre-intervention to 3-month follow-up (p =.017, d = 0.35), with larger increases in IL-6 production following MBSR compared to HEP. No study-related adverse events were reported. Results show that mindfulness training may be effective for boosting innate immunocompetence among lonely older adults. Given that immunocompetence tends to decline with age, mindfulness training may help to counteract the effects of aging and psychosocial stress on infection risk and recovery from injury.
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Atenção Plena , Expressão Gênica , Interleucina-6 , Solidão , Atenção Plena/métodos , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , Resultado do Tratamento , Humanos , Idoso , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Patients with primary malignant brain tumors have high symptom burden and commonly rely on family caregivers for practical and emotional support. This can lead to negative mental and physical consequences for caregivers. We investigated effectiveness of an 8-week nurse-led online needs-based support program (SmartCare©) with and without online self-guided cognitive behavioral therapy (CBT) for depression compared to enhanced care as usual (ECAU) on depressive symptoms, caregiving-specific distress, anxiety, mastery, and burden. METHODS: Family caregivers scoring ≥ 6 on a depressive symptoms inventory were randomized to three groups: ECAU plus self-guided CBT and SmartCare©; ECAU plus SmartCare©; ECAU only. Primary outcomes (depressive symptoms; caregiving-specific distress) and secondary outcomes (anxiety, caregiver mastery, and caregiver burden) were assessed online. Intention to treat (ITT) and per protocol (PP) analyses of covariance corrected for baseline scores were performed for outcomes at 4 months. RESULTS: In total, 120 family caregivers participated. Accrual and CBT engagement were lower than expected, therefore intervention groups were combined (n = 80) and compared to ECAU (n = 40). For depressive symptoms, no statistically significant group differences were found. Caregiving-specific distress decreased in the intervention group compared with ECAU (ITT: p = 0.01, partial ɳ2 = 0.08; PP: p = 0.02, partial ɳ2 = 0.08). A trend towards improvement in mastery for the intervention group compared with ECAU was identified (ITT: p = 0.08, partial ɳ2 = 0.04; PP: p = 0.07, partial ɳ2 = 0.05). CONCLUSIONS: SmartCare©, with or without self-guided CBT, reduced caregiving-specific distress with a trend towards improving mastery. SmartCare© has the potential to improve the lives of families coping with a brain tumor diagnosis. TRIAL REGISTRATION NUMBER: NCT02058745; 10 February 2014.
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Neoplasias Encefálicas , Terapia Cognitivo-Comportamental , Adaptação Psicológica , Ansiedade/terapia , Cuidadores , Humanos , Qualidade de VidaRESUMO
OBJECTIVE: Mindfulness interventions have been effective for improving a range of health outcomes; however, pathways underlying these effects remain unclear. Inflammatory processes may play a role, possibly through increased resistance of immune cells to the anti-inflammatory effects of glucocorticoids (i.e., glucocorticoid resistance, or GCR). Here, we conducted an initial examination of whether mindfulness training mitigates GCR among lonely older adults. METHODS: Lonely older adults (65-85 years; n = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or a matched Health Enhancement Program (HEP). Whole blood drawn before and after the intervention and at 3-month follow-up was incubated with endotoxin and varying concentrations of dexamethasone, and interleukin-6 production was assessed using enzyme-linked immunosorbent assay. GCR was assessed as the concentration of dexamethasone required to decrease the stimulated interleukin-6 response by 50% (half maximal inhibitory concentration), with higher concentrations indicating greater GCR. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects. RESULTS: There was no overall time by condition effect on GCR across all time points. However, a significant time by condition effect was observed from preintervention to postintervention (d = 0.29), such that MBSR buffered increases in GCR observed in the HEP group. Although MBSR showed small, nonsignificant reductions in GCR from preintervention to 3-month follow-up, group differences were not maintained at the 3-month follow-up (d = 0.10). CONCLUSIONS: Results suggest that MBSR may protect against declines in the sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids among at-risk lonely older adults and show value in studying this biological mechanism in future trials.Trial Registration: Clinical Trials identifier NCT02888600.
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Atenção Plena , Glucocorticoides , Interleucina-6 , Estresse Psicológico/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: Mothers of children with cancer confront life stress that can impact their psychological and physical health and, in turn, the health of the family. Recommendations advocate preemptive stress-management interventions; however, few studies have investigated their efficacy. Here, we report results of a parallel randomized pilot trial examining health benefits of a stress management intervention designed to teach coping skills. METHODS: One hundred twenty mothers (age 36 ± 8 years) of children newly diagnosed with cancer were randomized to a 12-session stress management intervention (n = 60) or usual care (n = 60). Sessions took place in the inpatient or outpatient setting of a children's hospital. Primary outcome variables included psychological function and physical health assessed preintervention and postintervention and at 6-month follow-up (â¼12 months postdiagnosis). RESULTS: Enrollment, retention, and satisfaction data supported feasibility and acceptability. Latent change score models showed the intervention reduced perceived stress (d = -0.37, p = 0.03), anxiety symptoms (ds = -0.38 and -0.56, ps < .03) and, a nonsignificant effect for depressive symptoms (d = -0.29, p = .11) across the 6 months following diagnosis. Intervention participants also endorsed fewer depressive symptoms than controls â¼12 months after diagnosis. The intervention improved stress management skills, which associated with the psychological benefits of participation. There were no intervention-related changes in perceived health or markers of inflammation. CONCLUSION: Intervention-related improvements in stress management skills may result in better psychological health in the face of caring for a child with cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02022449.
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BACKGROUND: Asthma is a common childhood illness with high morbidity and mortality among minority and socio-economically disadvantaged children. Disparities are not fully accounted for by differences in asthma prevalence, highlighting a need for interventions targeting factors associated with poorer asthma control. One such factor is psychological stress. OBJECTIVE: Here, we examine the feasibility and acceptability of "I Can Cope (ICC)," a school-based stress management and coping intervention for children with asthma. METHODS: A parallel randomized pilot trial was conducted. One hundred and four low-income children (mean age 10 years; 54% male; 70% African American) with persistent asthma were recruited from 12 urban schools and randomized to the following: (a) ICC or one of two control conditions: (b) "Open Airways for Schools (OAS)"-an asthma education intervention or (c) no treatment. RESULTS: Seventy one percentage of eligible children participated in the study, with a dropout rate of 12%. ICC was rated as highly acceptable by participating children and parents. Preliminary efficacy data suggest that when compared with no treatment, ICC resulted in decreased symptoms of depression, perceived stress and child-reported symptoms of asthma, and improvements in sleep quality and child-reported asthma control. There were no intervention-related changes in objective measures of asthma morbidity. The magnitude of intervention effects on psychological function did not differ between the ICC and OAS groups. CONCLUSIONS: Results support the feasibility and acceptability of utilizing school-based interventions to access hard to reach children with asthma. Preliminary findings offer support for future, large-scale efficacy studies of school-based interventions designed to target multiple factors that contribute to asthma disparities.
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Adaptação Psicológica , Asma/epidemiologia , Educação de Pacientes como Assunto , Instituições Acadêmicas , Estudantes , Adolescente , Asma/etiologia , Asma/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Serviços de Saúde Materno-Infantil , Projetos Piloto , Vigilância em Saúde Pública , Qualidade de Vida , Fatores Socioeconômicos , Estresse PsicológicoRESUMO
Childhood abuse confers risk for psychopathology and pathophysiology in midlife through intermediate pathways that remain unclear. Systemic inflammation was tested in the present study as one pathway that may link physical abuse in childhood to the adult functioning of corticolimbic brain circuits broadly implicated in risk for poor mental and physical health. Midlife adults (Nâ¯=â¯303; 30-51â¯years of age; 149 women) without psychiatric, immune, or cardiovascular diagnoses provided retrospective reports of childhood physical abuse. Functional connectivity between corticolimbic brain areas (amygdala, hippocampus, ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC]) was measured at rest using functional magnetic resonance imaging. Circulating levels of interleukin(IL)-6, a pro-inflammatory cytokine previously linked to childhood abuse and corticolimbic functionality, were measured via blood draw. Consistent with prior studies, retrospectively reported childhood physical abuse was associated positively with circulating IL-6, and negatively with connectivity between the amygdala and vmPFC. IL-6 was also associated negatively with several corticolimbic functional connections, including amygdala-vmPFC connectivity. Moreover, path analyses revealed an indirect effect of IL-6 that partially explained the association between childhood physical abuse and adult amygdala-vmPFC connectivity. Consistent with recent neurobiological models of early life influences on disease risk across the lifespan, associations between childhood physical abuse and adulthood corticolimbic circuit functionality may be partially explained by inflammatory processes.
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Maus-Tratos Infantis/psicologia , Inflamação/metabolismo , Vias Neurais/fisiopatologia , Adulto , Experiências Adversas da Infância , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiopatologia , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Criança , Conectoma/métodos , Feminino , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Inflamação/imunologia , Interleucina-6/análise , Interleucina-6/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Abuso Físico , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Estudos RetrospectivosRESUMO
Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates cellular sensitivity to GC-mediated anti-inflammatory signaling, thereby affecting levels of pro-inflammatory molecules. Thus, we hypothesized that extremes of self-reported sleep duration may covary with circulating levels of inflammatory markers as a function of allelic variation in NR3C1. Specifically, we examine the possibility that a single nucleotide polymorphism of the GR gene-(rs6198), the minor (G) allele of which confers reduced GR sensitivity-moderates an association of sleep duration with interleukin (IL)-6 and C-reactive protein (CRP) among a large sample (IL-6: Nâ¯=â¯857; CRP: Nâ¯=â¯929) of midlife community volunteers of European ancestry. Findings showed that sleep duration varied inversely with IL-6 (ßâ¯=â¯-0.087, pâ¯=â¯.012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (ßâ¯=â¯-0.071, pâ¯=â¯.039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: ßâ¯=â¯0.093, pâ¯=â¯.006), which was not moderated by rs6198 genotype. In conclusion, we show that a common genetic variant in the GR moderates an inverse association of self-reported sleep duration with circulating IL-6, possibly contributing to the increased disease risk observed among some short sleepers.
Assuntos
Receptores de Glucocorticoides/genética , Sono/genética , Adulto , Alelos , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Genótipo , Glucocorticoides/genética , Glucocorticoides/metabolismo , Haplótipos , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptores de Glucocorticoides/imunologia , Receptores de Glucocorticoides/metabolismo , Autorrelato , Sono/imunologiaRESUMO
AIMS AND OBJECTIVES: To examine and compare the differences in symptoms and symptom clusters between postmenopausal women with early-stage breast cancer who did and did not receive chemotherapy prior to aromatase inhibitor (AI) therapy. BACKGROUND: Women with breast cancer often experience multiple concurrent symptoms during AI therapy. The burden of symptoms prior to AI is associated with nonadherence to cancer treatment. To date, few studies have comprehensively explored the symptoms and symptom clusters occurring prior to AI therapy. DESIGN: Secondary analysis of a prospective repeated-measures study. METHODS: The sample comprised postmenopausal women (N = 339) with breast cancer who would receive AI therapy with or without chemotherapy. We collected information on 48 symptoms after surgery or chemotherapy but before AI therapy using different symptom assessment tools. Mann-Whitney U tests were used to compare the differences in the severity of symptoms between groups. Exploratory factor analysis (EFA) was conducted to determine symptom clusters. This study followed STROBE guidelines. RESULTS: The most severe symptoms among women with breast cancer prior to AI therapy were breast sensitivity, unhappy with the appearance of my body, general aches and pain, joint pain and muscle stiffness. Women who received chemotherapy prior to AI therapy experienced significantly higher severity of 22 symptoms than women who did not receive chemotherapy. Through EFA seven distinct symptom clusters were revealed in both groups: cognitive, musculoskeletal, psychological, vasomotor, weight, sexual and urinary, with additional gastrointestinal symptom cluster been identified in women who received chemotherapy. CONCLUSIONS: This study indicates the presence of symptoms among women with breast cancer prior to AI therapy, with higher severity of symptoms and greater number of symptom clusters for women who received chemotherapy. RELEVANCE TO CLINICAL PRACTICE: Nurses should assess and be aware of symptoms and symptom clusters existed prior to AI therapy and manage them in advance.