Jennifer M. Knight

Cortisol and Depressive Symptoms in a Population-Based Cohort of Midlife Women

Objective: To determine whether there is a relationship between depressive symptoms and cortisol assessed at first morning awakening, 6 PM, and 9 PM in a population-based sample of midlife women. If this relationship is not linear, we aim to test whether this relationship is nonlinear, only present in those with more severe depressive symptoms, better accounted for by diurnal slope, or only apparent under uncontaminated conditions. Methods: We investigated the cross-sectional association between cortisol and depressive symptoms, assessed by the Center for Epidemiological Studies Depression scale (CES-D) in 408 midlife women (45.7% African Americans, 54.3% white; mean age, 50.4 years) participating in the Chicago site of the Study of Womens Health Across the Nation. Results: Diurnal cortisol slope is significantly flatter for women with higher CES-D scores than for less depressed women (p < .05 for the interaction). This relationship remains significant even after adjusting for age, smoking status, race, education, income, menopausal status, hormone replacement therapy, body mass index, medications, and wake time, as well as possibly contaminating factors, including physical activity, smoking, eating, or caffeine or alcohol consumption before saliva collection. Results using depression assessed categorically (CES-D cutoff ≥16) were similar to those using continuous depression in both unadjusted and adjusted analyses (p = .005 for the interaction of CES-D by time). Conclusions: In this population-based sample of midlife women, greater depressive symptoms were associated with a significantly flatter diurnal cortisol slope than those with fewer symptoms, even after adjusting for covariates and possibly contaminating behaviors. BMI = body mass index; SWAN = Study of Womens Health Across the Nation; CES-D = Center for Epidemiologic Studies Depression scale; CRH = corticotropin-releasing hormone.

Toward Identifying the Effects of the Specific Components of Mindfulness-Based Stress Reduction on Biologic and Emotional Outcomes Among Older Adults

OBJECTIVES The objectives of this study were to examine the effects of specific Mindfulness-Based Stress Reduction (MBSR) activities (yoga, sitting and informal meditation, body scan) on immune function, circulating insulin-like growth factor (IGF)-1 concentrations, and positive affect among older adults. DESIGN The study design comprised longitudinal analyses of data from subjects in an 8-week MBSR program. SETTING The study was conducted at a University-affiliated health center. SUBJECTS This study involved 100 community-dwelling older adults. Inclusion criteria were as follows: ≥65 years of age and English-speaking. INTERVENTION This was an 8-week MBSR program. OUTCOME MEASURES Interleukin (IL)-6 and IGF-1 levels were assayed from blood collected at postintervention assessments. Participants were immunized postintervention with keyhole limpet hemocyanin (KLH), and immunoglobulin (Ig)M and IgG KLH-specific antibody responses were measured prior to immunization as well as 3 weeks and 24 weeks postintervention. Participants completed a 10-item measure of positive affect at study entry and postintervention. RESULTS Participants maintained weekly practice logs documenting participation in yoga, sitting meditation, informal meditation, and body scan. More practice of yoga was associated with higher post-treatment IGF-1 levels and greater improvement in positive affect from study entry to postintervention. Sitting meditation was positively associated with post-treatment IGF-1. Greater use of body scanning was associated with reduced antigen-specific IgM and IgG 3 weeks postintervention but not 24 weeks. No associations were found between MBSR activities and IL-6 levels. CONCLUSIONS Practice of MBSR activities, particularly yoga, could provide benefits for specific aspects of physiologic function and positive affect. Changes in adaptive immunity in older adult MBSR practitioners warrant further study.

Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients

Purpose: Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biologic mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves upregulation of proinflammatory genes and downregulation of genes involved in type I IFN response and antibody synthesis. Experimental Design: We compared pretransplant leukocyte CTRA gene expression between a group of 78 high versus low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. Results: Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA upregulation compared with matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity, including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. Conclusions: Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT. Clin Cancer Res; 22(1); 69–78. ©2015 AACR. See related commentary by Turcotte and Verneris, p. 6

Psychosocial factors and hematopoietic stem cell transplantation: Potential biobehavioral pathways

While psychosocial factors are known to affect cancer progression via biobehavioral pathways in many patient populations, these relationships remain largely unexplored in hematopoietic stem cell transplant (HCT) patients. The purpose of this paper is to critically review the literature regarding psychosocial and endocrine/immune aspects of HCT, with an emphasis on exploring pathways that may mediate the associations between psychosocial factors and disease outcomes. These include the roles of catecholamines, glucocorticoids, inflammation, vascular endothelial growth factor (VEGF), immune reconstitution and infectious susceptibility, as well as the new opportunities available in genomics research. We also discuss the implications for potential immunomodulating psychosocial interventions. Elucidating the biological pathways that account for the associations between psychosocial factors and clinical course could ultimately lead to improved outcomes for this psychologically and immunologically vulnerable population.

Patient‐reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902)

In hematopoietic cell transplantation (HCT), current risk adjustment strategies are based on clinical and disease‐related variables. Although patient‐reported outcomes (PROs) predict mortality in multiple cancers, they have been less well studied within HCT. Improvements in risk adjustment strategies in HCT would inform patient selection, patient counseling, and quality reporting. The objective of the current study was to determine whether pre‐HCT PROs, in particular physical health, predict survival among patients undergoing autologous or allogeneic transplantation.

Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation

To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.

Peri-Transplant Psychosocial Factors and Neutrophil Recovery following Hematopoietic Stem Cell Transplantation

Objective Multiple psychosocial factors appear to affect cancer progression in various populations; however, research investigating the relationship between psychosocial factors and outcomes following hematopoietic stem cell transplantation (HCT) is scarce. Subject to adverse immunological and psychological conditions, HCT patients may be especially vulnerable to psychosomatic health sequelae; therefore, we studied whether optimism and anxiety influence the pertinent clinical outcome of days to neutrophil engraftment (DTE). Method 54 adults undergoing either autologous or allogeneic HCT completed self-report questionnaires measuring optimism and anxiety. We assessed the association between these psychosocial variables and DTE. Results Greater optimism and less anxiety were associated with the favorable outcome of fewer DTE in autologous HCT recipients, though this relationship was no longer significant when reducing the sample size to only subjects who filled out their baseline survey by the time of engraftment. Conclusion Our findings are suggestive that optimism and anxiety may be associated with time to neutrophil recovery in autologous, but not allogeneic, adult HCT recipients. Further investigation in larger, more homogeneous subjects with consistent baseline sampling is warranted.

Patient-Reported Outcomes and Socioeconomic Status as Predictors of Clinical Outcomes after Hematopoietic Stem Cell Transplantation: A Study from the Blood and Marrow Transplant Clinical Trials Network 0902 Trial

This secondary analysis of a large, multicenter Blood and Marrow Transplant Clinical Trials Network randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes, including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pretransplantation Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores of the Short-Form 36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (P < .01 considered significant given multiple testing). Lower attained education was associated with increased distress (P = .002), lower income was related to worse physical functioning (P = .005) and increased distress (P = .008), lack of employment before transplantation was associated with worse physical functioning (P < .01), and unmarried status was associated with worse sleep (P = .003). In this large heterogeneous cohort of HCT recipients, although PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage.

Circulating endocannabinoids during hematopoietic stem cell transplantation: A pilot study.

Objective Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the eCB signaling system in a group of HCT recipients. Methods A total of 19 HCT recipients were enrolled and provided psychosocial data and blood samples at three peri-transplant time points: prior to transplant, hospital discharge, and approximately 100 days post-transplant. Psychosocial factors, inflammatory molecules, and the eCBs were determined and assessed for changes over this period and association with each other. Results HCT recipients demonstrated significant changes over the peri-transplant period in inflammatory molecules and psychosocial functioning, but not in circulating concentrations of the eCBs. Associations among these variables were most likely to be present pre-transplant and least likely to be present immediately post-transplant, with depressive symptoms and inflammation most significantly associated. The eCB 2-arachidonoylglycerol (2-AG) was significantly, positively associated with both interleukin (IL)-6 and C-reactive protein (CRP) and negatively associated with depressive symptoms. Conclusions The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

Pretransplantation Exercise and Hematopoietic Cell Transplantation Survival: A Secondary Analysis of Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0902)

Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0902 evaluated whether exercise and stress management training before hematopoietic cell transplantation (HCT) improved physical and mental functioning after HCT. Neither overall survival nor other patient-reported transplantation outcomes were improved by the training intervention. In some animal studies of HCT, moderate-intensity exercise for 8 weeks before HCT has been associated with positive effects on hematopoietic progenitors, resulting in improved donor engraftment and improved survival. Accordingly, we performed a secondary analysis of data from BMT CTN 0902 to determine whether exercise engagement before HCT was associated with engraftment and survival. We found no significant associations between self-reported pre-HCT exercise levels and engraftment or survival. There was also no effect of pretransplantation exercise on either neutrophil or platelet engraftment. These findings do not support the observations in animal models but are limited by several shortcomings that do not refute the hypothesis that exercise before HCT may be beneficial.