Sandra E. Sephton

Bio: Sandra E. Sephton is an academic researcher from University of Louisville. The author has contributed to research in topics: Breast cancer & Cancer. The author has an hindex of 37, co-authored 78 publications receiving 6515 citations. Previous affiliations of Sandra E. Sephton include Stanford University.

Diurnal Cortisol Rhythm as a Predictor of Breast Cancer Survival

Abstract: Background : Abnormal circadian rhythms have been observed in patients with cancer, but the prognostic value of such alterations has not been confirmed. We examined the association between diurnal variation of salivary cortisol in patients with metastatic breast cancer and subsequent survival. We explored relationships between cortisol rhythms, circulating natural killer (NK) cell counts and activity, prognostic indicators, medical treatment, and psychosocial variables. Methods Salivary cortisol levels of 104 patients with metastatic breast cancer were assessed at study entry at 0800, 1200, 1700, and 2100 hours on each of 3 consecutive days, and the slope of diurnal cortisol variation was calculated using a regression of log-transformed cortisol concentrations on sample collection time. NK cell numbers were measured by flow cytometry, and NK cell activity was measured by the chromium release assay. The survival analysis was conducted by the Cox proportional hazards regression model with two-sided statistical testing. Results Cortisol slope predicted subsequent survival up to 7 years later. Earlier mortality occurred among patients with relatively "flat" rhythms, indicating a lack of normal diurnal variation (Cox proportional hazards, P =. 0036). Patients with chest metastases, as opposed to those with visceral or bone metastases, had more rhythmic cortisol profiles. Flattened profiles were linked with low counts and suppressed activity of NK cells. After adjustment for each of these and other factors, the cortisol slope remained a statistically significant, independent predictor of survival time. NK cell count emerged as a secondary predictor of survival. Conclusions Patients with metastatic breast cancer whose diurnal cortisol rhythms were flattened or abnormal had earlier mortality. Suppression of NK cell count and NK function may be a mediator or a marker of more rapid disease progression.

The influence of bio-behavioural factors on tumour biology: pathways and mechanisms

Abstract: Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

Mindfulness meditation alleviates depressive symptoms in women with fibromyalgia: Results of a randomized clinical trial

Abstract: Objective Depressive symptoms are common among patients with fibromyalgia, and behavioral intervention has been recommended as a major treatment component for this illness. The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction (MBSR) intervention on depressive symptoms in patients with fibromyalgia. Methods This randomized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were randomly assigned to treatment (n = 51) or a waiting-list control group (n = 40). Eligible patients were at least 18 years old, willing to participate in a weekly group, and able to provide physician verification of a fibromyalgia diagnosis. Of 166 eligible participants who responded to local television news publicizing, 49 did not appear for a scheduled intake, 24 enrolled but did not provide baseline data, and 2 were excluded due to severe mental illness, leaving 91 participants. The sample averaged 48 years of age and had 14.7 years of education. The typical participant was white, married, and employed. Patients randomly assigned to treatment received MBSR. Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training. Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline, immediately postprogram, and at followup 2 months after the conclusion of the intervention. Results Change in depressive symptoms was assessed using slopes analyses of intervention effects over time. Depressive symptoms improved significantly in treatment versus control participants over the 3 assessments. Conclusion This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia.

Circadian disruption in cancer: a neuroendocrine-immune pathway from stress to disease?

Abstract: Psychosocial factors may modulate the course of cancer, but few data have been gathered on the biological mechanisms by which these effects may be mediated. We briefly review evidence of psychosocial effects on cancer progression and discuss one potential pathway that may underlie these effects: the disruption of neuroendocrine and immune circadian rhythms. Circadian system alterations occur in tumor tissue, tumor-bearing animals, and cancer patients with greater disruption seen in more advanced cases. Rhythm alterations include diminished amplitude, phase shifts, period changes, and erratic peaks and troughs in endocrine, metabolic, immunological, and rest- activity cycles. Psychosocial factors can engender dysregulation of circadian function. Cancer-related circadian dysregulation may also be driven by genetic factors, environmental and behavioral influences, and effects of the tumor on host clock regulation. There are several mechanisms by which circadian disruption might hasten tumor growth: via direct effects of altered hormone levels on tumor cells, effects on tumor versus host metabolism, neuroimmune effects resulting in cancer-relevant immunosuppression, or reduced efficacy and tolerability of cancer treatments for which the timing of administration is based upon the assumption of normal circadian rhythms. Emerging data in the human and animal literature suggest that circadian regulation may be an important prerequisite for the maintenance of host defenses against cancer. Thus, stress-related circadian disruption may have negative implications for cancer prognosis. Psychosocial effects on cancer progression may be measured, and possibly mediated, by disruption of circadian function.

The Effect of Mindfulness-Based Therapy on Anxiety and Depression: A Meta-Analytic Review

Abstract: Objective:Although mindfulness-based therapy has become a popular treatment, little is known about its efficacy. Therefore, our objective was to conduct an effect size analysis of this popular intervention for anxiety and mood symptoms in clinical samples.Method:We conducted a literature search using PubMed, PsycINFO, the Cochrane Library, and manual searches. Our meta-analysis was based on 39 studies totaling 1,140 participants receiving mindfulness-based therapy for a range of conditions, including cancer, generalized anxiety disorder, depression, and other psychiatric or medical conditions. Results:Effect size estimates suggest that mindfulness-based therapy was moderately effective for improving anxiety (Hedges’sg!0.63) and mood symptoms (Hedges’sg!0.59) from pre- to posttreatment in the overall sample. In patients with anxiety and mood disorders, this intervention was associated with effect sizes (Hedges’sg) of 0.97 and 0.95 for improving anxiety and mood symptoms, respectively. These effect sizes were robust, were unrelated to publication year or number of treatment sessions, and were maintained over follow-up.Conclusions:These results suggest that mindfulnessbased therapy is a promising intervention for treating anxiety and mood problems in clinical populations.

Psychological Stress and Disease

Abstract: Despite widespread public belief that psychological stress leads to disease, the biomedical community remains skeptical of this conclusion. In this Commentary, we discuss the plausibility of the belief that stress contributes to a variety of disease processes and summarize the role of stress in 4 major diseases: clinical depression, cardiovascular disease (CVD), human immunodeficiency virus (HIV)/AIDS, and cancer.

Construct Validity of the Five Facet Mindfulness Questionnaire in Meditating and Nonmeditating Samples.

Abstract: Previous research on assessment of mindfulness by self-report suggests that it may include five component skills: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience. These elements of mindfulness can be measured with the Five Facet Mindfulness Questionnaire (FFMQ). The authors investigated several aspects of the construct validity of the FFMQ in experienced meditators and nonmeditating comparison groups. Consistent with predictions, most mindfulness facets were significantly related to meditation experience and to psychological symptoms and well-being. As expected, relationships between the observing facet and psychological adjustment varied with meditation experience. Regression and mediation analyses showed that several of the facets contributed independently to the prediction of well-being and significantly mediated the relationship between meditation experience and well-being. Findings support the construct validity of the FFMQ in a combination of samples not previously investigated.

If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans.

Abstract: The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.

Social Support and Health: A Review of Physiological Processes Potentially Underlying Links to Disease Outcomes

Abstract: Social support has been reliably related to lower rates of morbidity and mortality. An important issue concerns the physiological mechanisms by which support influences such health endpoints. In this review, I examine evidence linking social support to changes in cardiovascular, neuroendocrine, and immune function. Consistent with epidemiological evidence, social support appears to be related to more positive “biological profiles” across these disease-relevant systems. Recent research on immune-mediated inflammatory processes is also starting to provide data on more integrative physiological mechanisms potentially linking social support to health. The implications of these links, along with future research directions are discussed.