Advancing the biobehavioral research of fatigue with genetics and genomics.
ABSTRACT: To examine phenotypic considerations in the study of fatigue and to explore significant issues affecting the extension of biobehavioral research of fatigue by the inclusion of genetic and genomic markers. THEORETICAL ORGANIZATION: Fatigue is a condition that has an adverse effect on quality of life that has been a focus of nursing inquiry. Yet, the study of fatigue has been stymied by the lack of phenotypic clarity. To expand the biobehavioral inquiry of fatigue, phenotypic clarity is needed. In addition, examining genomic factors associated with fatigue may help to elucidate the pathophysiology of fatigue and, in the future, lead to targeted interventions that address the molecular basis of fatigue.Given that nursing has been at the forefront of the study of fatigue, nurse scientists should consider enhancing phenotypic clarity by the development of a case-definition and use of a core measure of fatigue, one that can be augmented by condition- or population-specific measures as needed. Following the establishment of phenotypic clarity, the integration of genomics into biobehavioral research offers an opportunity for further clarity of phenotypes and for theoretical specification of the pathophysiology of conditions such as fatigue.The development of targeted interventions for fatigue depend on a more precise definition of fatigue and a better understanding of the biologic processes that contribute to its development and persistence.
Project description:BACKGROUND:Fatigue is one of the most common and disabling side effects of cancer and its treatment. Although research typically has focused on fatigue that occurs during and after treatment, patients may experience fatigue even before treatment onset. The current study was designed to identify biobehavioral risk factors associated with fatigue before adjuvant therapy in women with early-stage breast cancer. METHODS:Patients with stage 0 to stage IIIA breast cancer (270 women) were recruited before the onset of adjuvant or neoadjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy. Host factors that may influence fatigue were identified from an empirically based, biobehavioral model and assessed using self-report questionnaires, medical record review, and blood collection (for genetic data). Fatigue was assessed by questionnaire. Linear regression analyses were used to evaluate the association between host factors and dimensions of fatigue, with general fatigue as the primary dimension of interest. RESULTS:Fatigue was elevated at the pretreatment assessment compared with published controls. Bivariate analyses identified demographic, cancer-related, and biobehavioral correlates of fatigue. In the multivariable model, predictors of general fatigue included younger age, lower educational level, lower cancer stage, and history of childhood maltreatment (all P values <.05), with the full model accounting for approximately 18.4% of the variance in fatigue. Secondary analyses identified common and specific predictors of emotional, mental, and physical dimensions of fatigue. CONCLUSIONS:Among women who have not yet initiated treatment of breast cancer, demographic and psychosocial factors are associated with elevated fatigue and could be used to identify at-risk patients for early intervention.
Project description:OBJECTIVE:Fatigue is a common side effect of cancer treatment, but there is considerable variability in fatigue severity and persistence among survivors. This study aimed to characterize longitudinal trajectories of fatigue after breast cancer treatment and to identify predictors of varying fatigue trajectories. METHODS:Women (N = 191) from the Mind-Body Study completed assessments after primary treatment for early stage breast cancer and at regular follow-ups that occurred up to 6 years after treatment (M = 4.3 years). Growth mixture models were used to characterize fatigue trajectories, and demographic, medical, and biobehavioral risk factors were examined as predictors of trajectory group. RESULTS:Five trajectories were identified, characterized as High, Recovery, Late, Low, and Very Low fatigue. The High and Recovery groups (40% of sample) evidenced elevated fatigue at posttreatment that declined in Recovery but persisted in the High group. In bivariate analyses, trajectory groups differed significantly on depressive symptoms, sleep disturbance, childhood adversity, body mass index, and the inflammatory marker soluble TNF receptor type II, which were higher in the High and/or Recovery groups. In multivariate models, depressive symptoms and childhood adversity distinguished High and Recovery from other groups. Rates of chemotherapy were higher in the Recovery than in the High or Late group, whereas rates of endocrine therapy were higher in the High than in the Recovery group. CONCLUSIONS:There are distinct longitudinal trajectories of fatigue after breast cancer treatment. Psychological factors are strongly associated with adverse fatigue trajectories, and together with treatment exposures may increase risk for cancer-related fatigue. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Project description:This article reports the cross-studies analysis of projects from the P30 Center of Excellence for Biobehavioral Approaches to Symptom Management. Although the projects investigated diverse populations, a consistent theoretical and empirical approach guided each project.Common data elements included the following measures of psychobehavioral variables: the PROMIS Short-Form Fatigue Scale, the Center of Epidemiologic Studies Depression Scale, and the Perceived Stress Scale. Plasma cytokines were measured as the shared biological data element.Data were analyzed from 295 participants with fibromyalgia (n = 72), second trimester pregnancy (n = 73), sickle cell anemia (n = 60), and cardiometabolic risk (n = 91). The mean age of participants was 35.4 years, and the most participants were female. Levels of symptoms were generally elevated across samples; the level of fatigue ranged from 18.9 to 24.7, depressive symptoms from 12.5 to 23.4, and perceived stress from 16.5 to 21.8. Intercorrelations among symptom measures and perceived stress were strong across the samples. However, correlations among psychobehavioral variables and cytokines were variable, indicating a separate relationship for the measures with cytokines.Future work in symptom science could benefit from common data elements, including biomarkers, across populations to better develop the taxonomy of symptom profiles across conditions.
Project description:Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov.
Project description:A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms.All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later.Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values < 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values < 0.017).Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved.
Project description:Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.
Project description:To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial.Three hundred twenty-six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life and were followed up for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification.Sixty-nine individuals experienced a hospitalization or died over a mean follow-up period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (hazard ratio [HR] = 2.72 [95% confidence interval = 1.63-4.54], per stage); 6-minute walk (HR = 0.50 [0.34-0.73] per 500 ft), total steps (HR = 0.82 [0.71-0.94] per 1000 steps), high-sensitivity C-reactive protein (HR = 1.44 [1.01-2.06] per 4.5 mg/l), depression (HR = 1.12 [1.01-1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14-2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and 6-minute walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model.Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD.
Project description:A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment.
Project description:BACKGROUND:Testicular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients. METHODS:Participants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2. DISCUSSION:GET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors. TRIAL REGISTRATION:Clinicaltrials.gov, NCT04150848. Registered on 28 October 2019.
Project description:To evaluate the perceived usefulness of publicly reported nursing home quality indicators.Primary data were collected from October 2013 to August 2014 among a convenience sample of persons (or family member) recently admitted or anticipating admission to a nursing home within 75 miles of the city of Philadelphia.Structured interviews were conducted to assess the salience of data on the Medicare Nursing Home Compare website, including star ratings, clinical quality measures, and benchmarking of individual nursing home quality with state and national data.Interviews were transcribed verbatim, independently coded by two reviewers, and agreement determined. A thematic analysis of transcripts was undertaken.Thirty-five interviews were completed. Eighty-three percent (n = 29) were caregivers and 17 percent (n = 6) were residents. Star ratings, clinical quality measures, and benchmarking information were salient to decision making, with preferred formats varying across participants. Participants desired additional information on the source of quality data. Confusion was evident regarding the relationship between domain-specific and overall star quality ratings.The Nursing Home Compare website provides salient content and formats for consumers. Increased awareness of this resource and clarity regarding the definition of measures could further support informed decision making regarding nursing home choice.