A phenotype of resiliency? cross-sectional psychobiological differences between caregivers who are vulnerable vs. resilient to depression, and controls

Introduction: Being a caregiver of chronically ill children is a source of chronic-psychological stress affecting general physical and mental health. However, there is tremendous variance among caregivers: some may develop stress-related depression, whereas others are more “resilient”. The objective of the study was to phenotypically differentiate on psychobiology caregivers who developed depressive symptoms (“vulnerable”) vs. those who did not (“resilient”) from each other and from age-matched controls. Methods: Forty-five mothers of chronically-ill children and 18 controls have been examined. Caregivers were divided via a median split of Center for Epidemiological Studies Depression Scale scores in “resilient” (RCs) and “vulnerable” (VCs). We assessed cognitive, affective, metabolic, neuroendocrine and oxidative markers at rest and in response to a laboratory social stressor. ANCOVAs and Bonferroni post-hoc tests were used to examine between-group differences. Results: Although RCs compared to VCs had similar levels of objective parenting-related burden (P = 0.51), they had lower subjective distress (P < 0.01) and higher levels of positive affect (P = 0.04). Although RCs compared to controls had higher levels of objective parenting-related burden (P = 0.04), they had greater cortisol suppression post-dexamethasone (P = 0.05), lower F2-isoprostanes/vitamin E ratio (P < 0.01) and lower fasting insulin levels (P = 0.06). Discussion: Our results suggest that caregivers with higher resiliency demonstrate more salutary stress-related functioning in comparison with less resilient caregivers and, more surprisingly, non-caregiver controls. These findings might be interpreted in the spirit of Nietzsche's quote “What does not kill me, makes me stronger” and of the idea that successfully overcoming adversity may be more psychobiologically beneficial than not having been exposed to any adversity

Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999-2002.

Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT) levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48-2.65; OR 1.17, 95% CI 0.52-2.62, resp.). Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006-0.79) and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006-0.24). Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans

Maternal caregivers have confluence of altered cortisol, high reward-driven eating, and worse metabolic health.

Animal models have shown that chronic stress increases cortisol, which contributes to overeating of highly palatable food, increased abdominal fat and lower cortisol reactivity. Few studies in humans have simultaneously examined these trajectories. We examined premenopausal women, either mothers of children with a diagnosis of an autism spectrum disorder (n = 92) or mothers of neurotypical children (n = 91). At baseline and 2-years, we assessed hair cortisol, metabolic health, and reward-based eating. We compared groups cross-sectionally and prospectively, accounting for BMI change. Caregivers, relative to controls, had lower cumulative hair cortisol at each time point, with no decreases over time. Caregivers also had stable levels of poor metabolic functioning and greater reward-based eating across both time points, and evidenced increased abdominal fat prospectively (all ps ≤.05), independent of change in BMI. This pattern of findings suggest that individuals under chronic stress, such as caregivers, would benefit from tailored interventions focusing on better regulation of stress and eating in tandem to prevent early onset of metabolic disease, regardless of weight status

Trait mindfulness at baseline predicts increases in telomerase activity over time

Introduction Preliminary investigations of cross-sectional samples have linked trait mindfulness with measures related to the hypothalamic–pituitary–adrenal (HPA)-mediated stress response and to the inflammatory system, suggesting that this is one potential pathway linking mindfulness based interventions and health. However, no previous studies explored the association between the trait mindfulness construct and markers of cellular ageing. Methods In the current study we examined in a sample of healthy mothers (n = 92) of a child with Autism Spectrum Disorder (i.e. women showing high levels of chronic psychological stress) the prospective associations between a multidimensional scale of trait mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ), and telomerase activity (TA), a marker of cellular ageing and telomere homeostasis. Participants’ trait mindfulness and TA were assessed at baseline as well as 9 and 18 month follow-up. Results Analysis showed that higher levels of baseline mindfulness on FFMQ observation and describe subscales were related to increase in TA from baseline to 9 month (r = 0.27, P = 0.03 and r = 0.24, P = .04, respectively). Additionally, the FFMQ Describe subscale was related to increase in TA from baseline to 18 month (r = .30, P = .02). Results are reported following covariate adjustment of age, BMI, ethnicity, and education. Discussion Our results showed that higher levels of baseline mindfulness are associated with higher increases in TA after 9 months and 18 months, with increased TA reportedly being associated with decreased oxidative damage, increased telomere length and overall more functional cellular physiology. These findings support a role of mindfulness-related interventions to increase general and mental health

Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging: A descriptive study.

BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched "healthy" Body Mass Index (BMI) and "overweight"/"obese" BMI groups. RESULTS: Long-term human CR practitioners had lower BMI (p &lt;  0.001) and fasting glucose (p &lt;  0.001), as expected. They showed similar frequencies of pre-senescent cells (CD8+CD28- T cells and CD57 and PD-1 expressing T cells) to the comparison groups. Even after adjusting for covariates, including cytomegalovirus status, we observed shorter peripheral blood mononuclear cell telomeres in the CR group (p = 0.012) and no difference in granulocyte telomeres between groups (p = 0.42). CONCLUSIONS: We observed no clear evidence that CR as it is currently practiced in humans delays immune aging related to telomere length or T cell immunosenescent markers

More than a feeling: A unified view of stress measurement for population science.

Stress can influence health throughout the lifespan, yet there is little agreement about what types and aspects of stress matter most for human health and disease. This is in part because "stress" is not a monolithic concept but rather, an emergent process that involves interactions between individual and environmental factors, historical and current events, allostatic states, and psychological and physiological reactivity. Many of these processes alone have been labeled as "stress." Stress science would be further advanced if researchers adopted a common conceptual model that incorporates epidemiological, affective, and psychophysiological perspectives, with more precise language for describing stress measures. We articulate an integrative working model, highlighting how stressor exposures across the life course influence habitual responding and stress reactivity, and how health behaviors interact with stress. We offer a Stress Typology articulating timescales for stress measurement - acute, event-based, daily, and chronic - and more precise language for dimensions of stress measurement

Activation of multidrug efflux transporter activity at fertilization in sea urchin embryos (Strongylocentrotus purpuratus)

AbstractThis study presents functional and molecular evidence for acquisition of multidrug transporter-mediated efflux activity as a consequence of fertilization in the sea urchin. Sea urchin eggs and embryos express low levels of efflux transporter genes with homology to the multidrug resistance associated protein (mrp) and permeability glycoprotein (p-gp) families of ABC transporters. The corresponding efflux activity is low in unfertilized eggs but is dramatically upregulated within 25 min of fertilization; the expression of this activity does not involve de novo gene expression and is insensitive to inhibitors of transcription and translation indicating activation of pre-existing transporter protein. Our study, using specific inhibitors of efflux transporters, indicates that the major activity is from one or more mrp-like transporters. The expression of activity at fertilization requires microfilaments, suggesting that the transporters are in vesicles and moved to the surface after fertilization. Pharmacological inhibition of mrp-mediated efflux activity with MK571 sensitizes embryos to the toxic compound vinblastine, confirming that one role for the efflux transport activity is embryo protection from xenobiotics. In addition, inhibition of mrp activity with MK571 alone retards mitosis indicating that mrp-like activity may also be required for early cell divisions

Cortisol patterns are associated with T cell activation in HIV.

ObjectiveThe level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.MethodsWe studied 128 HIV-infected adults who were not on treatment and had a CD4(+) T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.ResultsLower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4(+) T cells (r = -0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8(+) T cells (r = -0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4(+) (r = 0.24, p = 0.018) and CD8(+) (r = 0.24, p = 0.017) activation.ConclusionsThese data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV