Anna L. Marsland

Psychosocial adjustment of siblings of children with cancer: a systematic review.

Objectives: To promote a broader understanding of the psychosocial impact of childhood cancer on siblings, a systematic review was undertaken. Directions for future research are proposed and clinical strategies are suggested for addressing the needs of these children.

Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults

BACKGROUND Converging animal findings suggest that higher peripheral levels of inflammation are associated with activation of central inflammatory mechanisms that result in hippocampal neurodegeneration and related impairment of memory function. We have recently shown, consistent with animal findings, an inverse association between peripheral levels of interleukin-6 (IL-6), a relatively stable marker of systemic inflammation, and memory function in mid-life adults. In the current study, we extend this work to test whether systemic inflammation is associated with reduced grey matter volume of the hippocampus. METHODS For this purpose, we used a computational structural neuroimaging method (optimized voxel-based morphometry) to evaluate the relationship between plasma IL-6 levels and hippocampal grey matter volume in a sample of 76 relatively healthy community volunteers ages 30-54. RESULTS Peripheral levels of IL-6 covaried inversely with hippocampal grey matter volume, and this relationship persisted after accounting for several possible confounders, including age, gender, race, years of education, percent body fat, blood pressure, smoking, physical activity, hours of sleep, alcohol use, and total grey matter volume. CONCLUSIONS To our knowledge, this is the first report of a relationship between a peripheral marker of IL-6 and hippocampal grey matter volume, raising the possibility that low-grade systemic inflammation could plausibly presage subclinical cognitive decline in part via structural neural pathways.

Family Adjustment to Childhood Cancer: A Systematic Review

This systematic review integrates qualitative and quantitative research findings regarding family changes in the context of childhood cancer. Twenty-eight quantitative, 42 qualitative, and one mixed-method studies were reviewed. Included studies focused on family functioning, marital quality, and/or parenting in the context of pediatric cancer, were written in English, and were published between 1996 and 2009. Overall, qualitative findings show that families alter roles, responsibilities, and day-to-day functioning to accommodate the needs of children with cancer. Although some degree of family reorganization is normative, the extent and impact of these changes varies. Quantitative work shows that mean levels of family functioning (e.g., cohesion, flexibility) are similar between families facing cancer and normative or comparison samples. However, families follow different trajectories of improvement, decline, or stability in family closeness and marital quality. Parenting has received limited quantitative research attention, but qualitative work suggests that parents perceive deeper bonds with ill children and may spoil or overprotect them. Conclusions support future work examining the influence of family-level variables on the adjustment of individual family members.

Cardiovascular reactivity and the course of immune response to an acute psychological stressor

&NA; This study evaluated the temporal nature of cellular immune responses, as well as the effects of cardiovascular reactivity on immune responses after exposure to an acute psychological stressor. Lymphocyte subsets and lymphocyte proliferative response to phytohemagglutinin were assessed at baseline and at 5 and 21 minutes after stressor onset in the experimental group and at the same time points in a nonstressor control group. By 5 minutes after stressor onset, the number of CD8 suppressor/cytotoxic T and CD16/56 natural killer cells increased and proliferative response to phytohemagglutinin decreased. These changes were maintained at 21 minutes. Those subjects showing the greatest cardiovascular reactivity had the largest immune alterations. These data did not indicate that gender significantly moderated immune responses. Results are consistent with the hypothesis that sympathetic activation mediates stressor‐induced quantitative alterations of peripheral blood lymphocyte subpopulations and nonspecific mitogen stimulated proliferation.

The Pathogenicity of Behavior and Its Neuroendocrine Mediation: An Example From Coronary Artery Disease

Although it is frequently hypothesized that perturbations of the bodys principal axes of neuroendocrine response, especially the sympathetic-adrenomedullary and pituitary-adrenocortical systems, mediate psychosocial influences on disease, evidence directly supporting this hypothesis is sparse at best and, for most disease entities, nonexistent. In this article, we illustrate a research strategy aimed at elucidating the role of behavior in disease pathogenesis by focusing on a single pathologic process--disease of the coronary vasculature--and emphasizing experimental evidence linking such disease to both behavior and sympathoadrenal activation in nonhuman primates. In cynomolgus monkeys, it is found that several psychosocial variables, e.g., social instability, behavioral dominance (in males), and subordination (in females), promote coronary atherogenesis, either independently or in interaction. Animals exhibiting a heightened cardiac responsivity to stress (reactions of probable sympathetic origin) also develop the most extensive coronary lesions and beta-adrenoreceptor blockade prevents the behavioral exacerbation of atherosclerosis. Social stress causes injury to arterial endothelium (also preventable by adrenoreceptor blockade) and, among chronically stressed animals, impairs endothelium-dependent vasomotor responses of the coronary arteries. It is suggested that similar research programs might elucidate the influence of behavior and neuroendocrine factors on the pathogenesis of other disease states and conditions, including susceptibility to infection.

Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers

Objective: Recent evidence suggests that higher peripheral levels of interleukin 6 (IL-6) are associated with poorer cognitive function and predict future cognitive decline among the elderly. The current investigation extends the study of relationships between plasma IL-6 and cognitive performance to healthy middle-aged adults and to an examination of more specific cognitive domains. Methods: Five hundred relatively healthy community volunteers aged 30 to 54 had blood drawn for the determination of plasma IL-6 levels and completed a battery of neuropsychological tests evaluating memory and executive function. Results: After controlling for age, gender, race, and education, hierarchical regression analyses revealed an inverse relationship between circulating levels of IL-6 and performance on clusters of tests assessing auditory recognition memory, attention/working memory, and executive function. In contrast, there was no association between IL-6 and performance on tests of general memory. Secondary analyses demonstrated that relationships between IL-6 and auditory recognition and working memory and executive function were independent of a number of health factors, including body mass index, smoking, and hypertension. Conclusions: These findings contribute to a growing body of evidence linking chronic inflammation to poorer cognitive functioning and extend these findings to a midlife community sample, raising the possibility that IL-6 may represent a biomarker for risk of future cognitive decline. IL = interleukin; CNS = central nervous system; BMI = body mass index; WMS = Wechsler Memory Scale; BP = blood pressure.

Stress, immune reactivity and susceptibility to infectious disease

Psychological stress is known to affect immune function and to predict infectious disease susceptibility. However, not all individuals who are stressed develop disease. In the present article, we report on a series of studies from our laboratory describing interindividual variability of immune responses to psychological stress. In our initial series of experimental investigations, we demonstrated that acute laboratory stress alters both quantitative and functional components of cellular immunity. An examination of response variability revealed that individuals differ substantially in the magnitude of these immune responses. These differences were found to parallel (and be predicted by) interindividual variability in stress-induced sympathetic nervous system activation. Further investigation revealed that individuals vary consistently in the magnitude of their immune responses to stress, making it conceivable that individual differences in immune reactivity provide a vulnerability factor mediating relationships between stress and disease. In support of this possibility, we have recently reported initial evidence that individual differences in the magnitude of stress-induced reduction of immune function may be of clinical significance, being related to an immune response relevant for protection against infection, antibody response to hepatitis B vaccination.

Negative emotions and acute physiological responses to stress

One pathway through which stressors are thought to influence physiology is through their effects on emotion. We used meta-analytic statisitical techniques with data from nine studies to test the effects of acute laboratory stressors (speech, star mirror-image tracing, handgrip) on emotional (undifferentiated negative emotion, anger, anxiety) and cardiovascular (CV) response. In all of the studies, participants responded to stressors with both increased CV response and increased negative emotion. Increases in negative emotion were associated with increases in CV response across tasks, however, these associations were small. The range of variance accounted for was between 2% and 12%. Thus, the contribution of negative emotion, as assessed in these studies, to physiological responses to acute laboratory stressors was limited. Although these results raise questions about the role of emotion in mediating stress-elicited physiological responses, the nature of the acute laboratory stress paradigm may contribute to the lack of a strong association.

How Disturbed Sleep May Be a Risk Factor for Adverse Pregnancy Outcomes A Hypothesis

Adverse pregnancy outcomes associated with significant maternal and infant morbidity are on the rise in Western society despite advances of medical technology. Current risk factors are insufficient to identify women at greatest risk of developing an adverse outcome. An attempt to identify novel contributors to increased risk is warranted. Sleep disturbances are frequent during pregnancy, yet are often dismissed as irrelevant. Emerging evidence indicates that sleep disturbances are associated with poor health outcomes, including cardiovascular disease. Disturbed sleep is also linked with an increased inflammatory response. Increased inflammation is proposed as a key biological pathway through which chronic disease and adverse pregnancy outcomes develop. In this paper, we propose a model and a testable hypothesis of how disturbed sleep in the first 20 weeks of pregnancy could contribute to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, and preterm birth via increased inflammation. Target Audience: Obstetricians & Gynecologists, Family Physicians Leaning Objectives: After completion of this article, the reader should be able to outline data linking sleep disturbances with an increased risk of some systemic disorders, recall characteristics of pregnancy complications which support the hypothesis that sleep disturbances may be related to these pregnancy outcomes, and summarize the likelihood and types of sleep disturbances that are common in pregnant women.

Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults.

Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance.