Dina Tell

Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer

Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.

Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.

IntroductionThis pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery.MethodsWomen (N = 30) with early-stage breast cancer received either PBRT, Mammosite brachytherapy at dose of 34 Gy 10 fractions/5 days, (N = 15) or WBRT, 3-D conformal techniques at dose of 50 Gy +10 Gy Boost/30 fractions, (N = 15). Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need. Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy. At each assessment, blood was obtained for determination of NKCA and the following instruments were administered: Perceived Stress Scale (PSS), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Functional Assessment of Cancer Therapy-General (FACT-G). Hierarchical linear modeling (HLM) was used to evaluate group differences in initial outcomes and change in outcomes over time.ResultsFatigue (FACT-F) levels, which were similar prior to radiation therapy, demonstrated a significant difference in trajectory. Women who received PBRT reported progressively lower fatigue; conversely fatigue worsened over time for women who received WBRT. No difference in perceived stress was observed between women who received PBRT or WBRT. Both groups of women reported similar levels of quality of life (FACT-G) prior to initiation of radiation therapy. However, HLM analysis revealed significant group differences in the trajectory of quality of life, such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy; whereas women receiving WBRT showed a decreasing trajectory. NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy.ConclusionsCompared to WBRT, PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy. Additionally, better quality of life predicts higher NKCA against tumor targets, emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy.

Relationship of childhood adversity and neighborhood violence to a proinflammatory phenotype in emerging adult African American men: An epigenetic link

African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity. The purpose of this study was to evaluate the extent to which exposure to early life adversity influences the psychological, cortisol, and proinflammatory response to acute stress (Trier Social Stress Test - TSST) in emerging adult AAM, ages 18-25years (N=34). Hierarchical linear modeling was used to examine the cortisol and IL-6 pattern of response to the TSST with respect to childhood adversity factors and DNA methylation of the IL-6 promoter. Findings revealed that in response to the TSST, greater levels of childhood trauma and indirect exposure to neighborhood violence were associated with a greater TSST-induced IL-6 response, and a blunted cortisol response. Reduced methylation of the IL6 promoter was related to increased exposure to childhood trauma and greater TSST-induced IL-6 levels. These results support the concept that exposure to childhood adversity amplifies the adult proinflammatory response to stress, which is related to epigenetic signature.

Day-to-day dynamics of associations between sleep, napping, fatigue, and the cortisol diurnal rhythm in women diagnosed as having breast cancer.

Objectives To examine whether day-to-day variations in sleep behaviors, ongoing sleep disturbance, and fatigue predict the cortisol diurnal rhythm in women recently diagnosed as having early-stage breast cancer. Methods Women (N = 130, mean [standard deviation] age = 55.6 [9.4] years) collected saliva 5×/day/2 days for cortisol. Diaries were used to assess prior-day nap duration, nocturnal awakenings, sleep latency, and morning restfulness. Ongoing fatigue and sleep disturbance were measured using the Multidimensional Fatigue Symptom Inventory and the Pittsburg Sleep Quality Inventory. Data were analyzed using a multilevel growth curve modeling. Results Greater ongoing fatigue (b = 0.035, p = .032), or sleep disturbance (b = 0.026, p = .006) predicted a slower cortisol decline. Greater ongoing fatigue also predicted higher awakening cortisol (b = 0.154, p = .030) and lower cortisol awakening response (CAR; b = −0.146, p = .005). Longer prior-day naps predicted higher CAR (b = 0.042, p = .050) and a steeper cortisol decline (b = −0.035, p = .003). Longer sleep latency predicted both a greater cortisol linear decline (b = −0.013, p < .001) and a greater quadratic slope curvature (b = 0.0007, p < .001). Feeling less rested in the morning predicted lower awakening cortisol (b = −0.187, p = .004), higher CAR (b = 0.124, p = .016), and a slower cortisol decline (b = 0.023, p = .042). Conclusions Both daily variations in sleep behaviors and ongoing sleep disturbance and fatigue are associated with a disrupted cortisol rhythm. In contrast, prior-day napping is associated with a more robust cortisol rhythm. These findings are particularly relevant to women with breast cancer who often experience sleep disturbance and fatigue. Additional research is needed to determine causal pathways between sleep disturbance and dysregulation of the hypothalamic-pituitary-adrenal axis in patients with breast cancer.

Recognition of Emotion from Facial Expressions with Direct or Averted Eye Gaze and Varying Expression Intensities in Children with Autism Disorder and Typically Developing Children

Eye gaze direction and expression intensity effects on emotion recognition in children with autism disorder and typically developing children were investigated. Children with autism disorder and typically developing children identified happy and angry expressions equally well. Children with autism disorder, however, were less accurate in identifying fear expressions across intensities and eye gaze directions. Children with autism disorder rated expressions with direct eyes, and 50% expressions, as more intense than typically developing children. A trend was also found for sad expressions, as children with autism disorder were less accurate in recognizing sadness at 100% intensity with direct eyes than typically developing children. Although the present research showed that children with autism disorder are sensitive to eye gaze direction, impairments in the recognition of fear, and possibly sadness, exist. Furthermore, children with autism disorder and typically developing children perceive the intensity of emotional expressions differently.

Quality of life in women who use pessaries for longer than 12 months.

Objectives Pessaries are an effective treatment for pelvic organ prolapse and urinary incontinence; however, few data exist describing long-term pessary use. Our aim was to describe symptom bother and quality of life (QoL) in women using pessaries for urinary incontinence and/or prolapse for at least 12 months. Methods Consecutive women who met inclusion criteria were approached for this observational cross-sectional study. Wilson and Cleary’s Health-Related Quality of Life Model guided the inclusion of biologic, functional, and individual factors that impact the health-related QoL. Consenting participants completed a generalized QoL index, the Center for Epidemiologic Depression Symptoms, Medical Outcomes Study Social Support Survey, and condition-specific measures; the Pelvic Floor Distress Inventory (PFDI-20-SF) and the Pelvic Floor Impact Questionnaire. Results Fifty-six women, mean age 74.4 years (range, 47–89 years), completed the survey. Mean length of time for pessary use was 4.5 years (1–15 years). Most of the women (n = 31, 55.4%) returned to the clinic for pessary care every 3 months. There was no difference in generalized QoL nor condition-specific total PFDI-20 in women performing self-care versus routine follow-up. Almost one third (29%) of participants reported complications related to pessary use (eg, vaginal erosion), and 41%were considering surgical repair in the near future. Women who were considering surgery had higher PFDI-20 scores relating to more bothersome prolapse symptoms than those not considering surgery (Pelvic Organ Prolapse Distress Inventory 6, 33.91 vs 24.73, P = 0.03). Conclusions Pessaries can be used to control pelvic floor symptoms for extended periods. Complication rates in this study were lower than previously reported, even in women not doing self-care. Not surprisingly, women considering surgical intervention reported greater symptom bother despite pessary use.

Triathlete Risk of Pelvic Floor Disorders, Pelvic Girdle Pain, and Female Athlete Triad.

Objectives Our primary objective was to describe the prevalence of pelvic floor disorders (PFDs), pelvic girdle pain (PGP), and the female athlete triad (disordered eating, menstrual irregularities, and osteoporosis) in a female triathlete population. We also evaluated for an association between these conditions. Methods We administered an online survey to women who self-identified as female triathletes. Using validated questionnaires, Epidemiology of Prolapse and Incontinence Questionnaire and Pelvic Girdle Questionnaire, along with the female athlete triad questionnaire, we identified the prevalence of PFDs, PGP, and female athlete triad in this specific population. Demographic and exercise intensity were also queried to characterize these female triathletes. Results Three hundred eleven female triathletes responded to the Internet survey. There was a significant prevalence of PFDs with stress urinary incontinence and anal incontinence symptoms being most common (37.4% and 28%, respectively). Urgency urinary incontinence and pelvic organ prolapse were less common (16% and 5%, respectively). Stress urinary incontinence and pelvic organ prolapse were more common in parous triathletes (P = 0.001, P = 0.05). Pelvic girdle pain was noted in 18% of these triathletes but was not disabling. Twenty-four percent of participants screened positive for at least 1 arm of the female athlete triad. No association was found between the female athlete triad and PFDs. Conclusions Pelvic floor disorders are common and bothersome in female triathletes. Pelvic girdle pain, while present, does not limit these athletes from their training. These female triathletes may be at risk for the female athlete triad. Female triathletes may be at risk for both metabolic and PFDs and should be screened when identified.

The Man I Once Knew: Grief and Inflammation in Female Partners of Veterans With Traumatic Brain Injury

Grief, although traditionally conceptualized as a bereavement-related reaction, is also experienced by significant others in response to the profound cognitive and personality changes associated with a traumatic brain injury (TBI) in a loved one. Grief associated with the death of a loved one is related to increases in proinflammatory cytokines, yet it is not clear whether this is the case for grief experienced by individuals caring for a significant other with TBI. The purpose of this cross-sectional, exploratory study was to examine grief and its association with a proinflammatory cytokine, tumor necrosis factor α (TNF-α), in wives/partners caring for veterans with TBI. Participants completed written measures of grief, perceived stress, and depressive symptoms and provided morning saliva samples for TNF-α analysis. Participants reported levels of grief comparable to those reported in studies evaluating individuals grieving the death of a loved one. Path analysis revealed that grief was not associated with TNF-α; however, participants reporting high levels of blame/anger, a subscale of the grief scale, had higher levels of TNF-α. In addition, both grief and blame/anger were related to increased perceived stress and depressive symptoms; however, path analysis demonstrated that perceived stress and depressive symptoms did not mediate the influence of blame/anger on TNF-α. These findings suggest that blame/anger associated with grief may be related to the elevations in TNF-α exhibited by individuals caring for a loved one with TBI.

Emotion recognition from congruent and incongruent emotional expressions and situational cues in children with autism spectrum disorder

In this research, the emotion recognition abilities of children with autism spectrum disorder and typically developing children were compared. When facial expressions and situational cues of emotion were congruent, accuracy in recognizing emotions was good for both children with autism spectrum disorder and typically developing children. When presented with facial expressions incongruent with situational cues, children with autism spectrum disorder relied more on facial cues than situational cues, whereas typically developing children relied more on situational cues. The exception was fear. When presented with incongruent information (i.e. a smiling boy surrounded by a swarm of bees), most children based their response on the situation and indicated that the boy felt scared. While the majority of typically developing children commented on the disparity between facial expressions and situational cues, children with autism spectrum disorder did not mention the conflicting cues. Although typically developing children were more accurate in recognizing emotion with situational cues, children with autism spectrum disorder were still adequate at identifying emotion from situational cues alone. These findings suggest that children with autism spectrum disorder show an understanding of simple emotions in prototypical situations, but may prefer facial expressions when facial expressions and situational cues are incongruent. Reasons for these findings are discussed.

During stress, heart rate variability moderates the impact of childhood adversity in women with breast cancer

Abstract Childhood adversity has long-lasting neuro-biological effects that can manifest as exaggerated stress responsivity to environmental challenge. These manifestations include a dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis as well as increased levels of inflammatory mediators in response to stress. In this investigation, vagal parasympathetic activity was assessed for its capacity to moderate the relationship between childhood adversity and stress responsivity (cortisol and inflammation) during an acute laboratory challenge (Trier Social Stress Test–TSST). Thirty women recently diagnosed with breast cancer underwent the TSST during which their heart rate was recorded and saliva samples collected for measurement of cortisol and the proinflammatory cytokine, IL-6. Vagal activity during the TSST was calculated as the high-frequency (HF) component of heart rate variability (HRV). Vagal activity during the TSST moderated the effect of childhood adversity on both the cortisol and the IL-6 response. Women who had lower vagal stress-reactivity during the TSST and reported greater childhood adversity showed a larger rise in cortisol and IL-6 when compared to women with lower childhood adversity. The findings demonstrate that women with exposure to childhood adversity and low vagal stress-reactivity (reduced parasympathetic activity) exhibit an elevated stress response characterized by greater cortisol and proinflammatory cytokine release. Inflammatory burden and HPA dysregulation subsequent to stress may impair cancer control.