Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study.

We studied peripheral leukocyte telomere length (LTL) as a predictor of antidepressant response to PPAR-γ agonist in patients with unremitted depression. In addition we examined correlation between LTL and the insulin resistance (IR) status in these subjects. Forty-two medically stable men and women ages 23-71 with non-remitted depression participated in double-blind placebo-controlled add-on of Pioglitazone to treatment-as-usual. Oral glucose tolerance tests were administered at baseline and at 12 weeks. Diagnostic evaluation of psychiatric disorders was performed at baseline and mood severity was followed weekly throughout the duration of the trial. At baseline, no differences in LTL were detected by depression severity, duration or chronicity. LTL was also not significantly different between insulin-resistant and insulin-sensitive subjects at baseline. Subjects with longer telomeres exhibited greater declines in depression severity in the active arm, but not in a placebo arm, P=0.005, r=-0.63, 95% confidence interval (95% CI)=(-0.84,-0.21). In addition, LTL predicted improvement in insulin sensitivity in the group overall and did not differ between intervention arms, P=0.036, r=-0.44, 95% CI=(-0.74,0.02) for the active arm, and P=0.026, r=-0.50, 95% CI=(-0.78,-0.03) for the placebo arm. LTL may emerge as a viable predictor of antidepressant response. An association between insulin sensitization and LTL regardless of the baseline IR status points to potential role of LTL as a non-specific moderator of metabolic improvement in these patients

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

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

Rapid Assessment of Reward-Related Eating: The RED-X5.

OBJECTIVE:The prevalence of obesity has created a plethora of questionnaires characterizing psychological aspects of eating behavior, such as reward-related eating (RRE). The Reward-based Eating Drive questionnaires (RED-9, RED-13) broadly and deeply assess the RRE construct. However, large-sample research designs require shorter questionnaires that capture RRE quickly and precisely. This study sought to develop a brief, reliable, and valid version of the RED questionnaire. METHODS:All-subset correlation was used to find a subset that maximally associated with the full RED-13 in two separate samples. Results were validated in a third independent sample. Internal consistency, test-retest reliability, and ability to explain variance in external outcomes were also assessed. RESULTS:A five-item questionnaire (RED-X5) correlated strongly with RED-13 in the independent sample (r = 0.95). RED-X5 demonstrated high internal consistency (omega total ≥ 0.80) and 6-month test-retest reliability (r = 0.72). RED-X5 accurately reproduced known associations between RED-13 and BMI, diabetes status, and craving for sweet and savory foods. As a novel finding, RED questionnaires predicted laboratory intake of chips. CONCLUSIONS:RED-X5 is a short, reliable, and valid measure of the RRE construct and can be readily implemented in large-sample research designs in which questionnaire space is limited

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

Indirect effect of financial strain on daily cortisol output through daily negative to positive affect index in the Coronary Artery Risk Development in Young Adults Study

Daily affect is important to health and has been linked to cortisol. The combination of high negative affect and low positive affect may have a bigger impact on increasing HPA axis activity than either positive or negative affect alone. Financial strain may both dampen positive affect as well as increase negative affect, and thus provides an excellent context for understanding the associations between daily affect and cortisol. Using random effects mixed modeling with maximum likelihood estimation, we examined the relationship between self-reported financial strain and estimated mean daily cortisol level (latent cortisol variable), based on six salivary cortisol assessments throughout the day, and whether this relationship was mediated by greater daily negative to positive affect index measured concurrently in a sample of 776 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants. The analysis revealed that while no total direct effect existed for financial strain on cortisol, there was a significant indirect effect of high negative affect to low positive affect, linking financial strain to elevated cortisol. In this sample, the effects of financial strain on cortisol through either positive affect or negative affect alone were not significant. A combined affect index may be a more sensitive and powerful measure than either negative or positive affect alone, tapping the burden of chronic financial strain, and its effects on biology

Indirect effect of financial strain on daily cortisol output through daily negative to positive affect index in the Coronary Artery Risk Development in Young Adults Study

Daily affect is important to health and has been linked to cortisol. The combination of high negative affect and low positive affect may have a bigger impact on increasing HPA axis activity than either positive or negative affect alone. Financial strain may both dampen positive affect as well as increase negative affect, and thus provides an excellent context for understanding the associations between daily affect and cortisol. Using random effects mixed modeling with maximum likelihood estimation, we examined the relationship between self-reported financial strain and estimated mean daily cortisol level (latent cortisol variable), based on six salivary cortisol assessments throughout the day, and whether this relationship was mediated by greater daily negative to positive affect index measured concurrently in a sample of 776 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants. The analysis revealed that while no total direct effect existed for financial strain on cortisol, there was a significant indirect effect of high negative affect to low positive affect, linking financial strain to elevated cortisol. In this sample, the effects of financial strain on cortisol through either positive affect or negative affect alone were not significant. A combined affect index may be a more sensitive and powerful measure than either negative or positive affect alone, tapping the burden of chronic financial strain, and its effects on biology

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