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1.  Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity 
The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress (“hormetic stress”). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses (“toxic stress”) and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease.
PMCID: PMC4022128  PMID: 24833580
Aging; Stress resistance; Resilience; Stressors; Psychological stress.
3.  Associations of ghrelin with eating behaviors, stress, metabolic factors, and telomere length among overweight and obese women: Preliminary evidence of attenuated ghrelin effects in obesity? 
Appetite  2014;76:84-94.
Ghrelin regulates homeostatic food intake, hedonic eating, and is a mediator in the stress response. In addition, ghrelin has metabolic, cardiovascular, and anti-aging effects. This cross-sectional study examined associations between total plasma ghrelin, caloric intake based on 3 day diet diaries, hedonic eating attitudes, stress-related and metabolic factors, and leukocyte telomere length in overweight (n=25) and obese women (n=22). We hypothesized associations between total plasma ghrelin and eating behaviors, stress, metabolic, cardiovascular, and cell aging factors among overweight women, but not among obese women due to lower circulating ghrelin levels and/or central resistance to ghrelin. Confirming previous studies demonstrating lowered plasma ghrelin in obesity, ghrelin levels were lower in the obese compared with overweight women. Among the overweight, ghrelin was positively correlated with caloric intake, giving in to cravings for highly palatable foods, and a flatter diurnal cortisol slope across 3 days. These relationships were non-significant among the obese group. Among overweight women, ghrelin was negatively correlated with insulin resistance, systolic blood pressure, and heart rate, and positively correlated with telomere length. Among the obese subjects, plasma ghrelin concentrations were negatively correlated with insulin resistance, but were not significantly correlated with blood pressure, heart rate or telomere length. Total plasma ghrelin and its associations with food intake, hedonic eating, and stress are decreased in obesity, providing evidence consistent with the theory that central resistance to ghrelin develops in obesity and ghrelin’s function in appetite regulation may have evolved to prevent starvation in food scarcity rather than cope with modern food excess. Furthermore, ghrelin is associated with metabolic and cardiovascular health, and may have anti-aging effects, but these effects may be attenuated in obesity.
PMCID: PMC4170078  PMID: 24462487
4.  Anger Is Associated with Increased IL-6 Stress Reactivity in Women, But Only Among Those Low in Social Support 
Social connections moderate the effects of high negative affect on health. Affective states (anger, fear, and anxiety) predict interleukin-6 (IL-6) reactivity to acute stress; in turn, this reactivity predicts risk of cardiovascular disease progression.
Here, we examined whether perceived social support mitigates the relationship between negative affect and IL-6 stress reactivity.
Forty-eight postmenopausal women completed a standardized mental lab stressor with four blood draws at baseline and 30, 50, and 90 min after the onset of the stressor and anger, anxiety, and fear were assessed 10 min after task completion. Participants self-rated levels of social support within a week prior to the stressor.
Only anger was related to IL-6 stress reactivity—those experiencing high anger after the stressor had significant increases in IL-6. IL-6 reactivity was marginally associated with perceived support, but more strikingly, perceived support mitigated anger associations with IL-6 stress reactivity.
Supportive ties can dampen the relationship of anger to pro-inflammatory reactivity to acute stress. Implications to cardiovascular disease are discussed.
PMCID: PMC4406249  PMID: 24357433
Social support; Anger; Stress reactivity; Interleukin-6
5.  Poor sleep quality potentiates stress-induced cytokine reactivity in postmenopausal women with high visceral abdominal adiposity 
Brain, behavior, and immunity  2013;S0889-1591(13)00464-9 10.1016/j.bbi.2013.09.010.
Sleep disturbance is a key behavioral risk factor for chronic medical conditions observed at high rates among overweight and obese individuals. Systemic inflammation, including that induced by stress, may serve as a common biological mechanism linking sleep, adiposity, and disease risk. To investigate these relationships, 48 postmenopausal women (mean age=61.8) completed a standardized laboratory stress task during which time blood was collected at baseline and 30+, 50+ and 90+ minutes after stressor onset to assess circulating levels of interleukin (IL)-6, IL-10, and IL-6/IL-10 ratio. Self-reported global sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) while adiposity was estimated by body mass index. Sagittal diameter was obtained in clinic to estimate visceral abdominal adiposity. Multi-level growth curve models revealed that poorer self-reported sleep quality was associated with greater stress-induced increases in IL-6/IL-10 ratio. In terms of adiposity, higher sagittal diameter, but not BMI, was associated with greater IL-6 reactivity (p’s<0.05). Further, associations between sleep quality and cytokine reactivity varied as a function of sagittal diameter. Among poor sleepers (1 SD above mean of PSQI score), stress-induced increases in IL-6 and IL-6/IL-10 ratio were significantly steeper in those with high visceral adiposity (1 SD above the mean of sagittal diameter) compared to those with low visceral adiposity (1 SD below the mean of sagittal diameter). In sum, poorer sleep quality and greater visceral adiposity, separately and especially in combination, are associated with greater stress-related increases in systemic inflammation. This research may help elucidate the complex link between sleep, obesity and inflammatory disease risk.
PMCID: PMC3962521  PMID: 24060585
6.  Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging 
Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals.
PMCID: PMC4361087  PMID: 23127296
Anxiety; Attentional bias; Cellular aging; Diseases of aging; Hypothalamic-pituitary-adrenal axis; Inflammation; Information processing; Neurobiological; Parasympathetic nervous system; Psychoneuroimmunology; Sympathetic nervous system; Threat
7.  A New Biomarker of Hedonic Eating? A Preliminary Investigation of Cortisol and Nausea Responses to Acute Opioid Blockade 
Appetite  2013;74:92-100.
Overweight and obese individuals differ in their degree of hedonic eating. This may reflect adaptations in reward-related neural circuits, regulated in part by opioidergic activity. We examined an indirect, functional measure of central opioidergic activity by assessing cortisol and nausea responses to acute opioid blockade using the opioid antagonist naltrexone in overweight/obese women (mean BMI = 31.1 ± 4.8) prior to the start of a mindful eating intervention to reduce stress eating. In addition, we assessed indices of hedonic-related eating, including eating behaviors (binge eating, emotional eating, external eating, restraint) and intake of sweets/desserts and carbohydrates (Block Food Frequency); interoceptive awareness (which is associated with dysregulated eating behavior); and level of adiposity at baseline. Naltrexone-induced increases in cortisol were associated with greater emotional and restrained eating and lower interoceptive awareness. Naltrexone-induced nausea was associated with binge eating and higher adiposity. Furthermore, in a small exploratory analysis, naltrexone-induced nausea predicted treatment response to the mindful eating intervention, as participants with more severe nausea at baseline maintained weight whereas those without nausea responses tended to gain weight. These preliminary data suggest that naltrexone-induced cortisol release and nausea may help identify individuals who have greater underlying food reward dependence, which leads to an excessive drive to eat. Future research is needed to confirm this finding and to test if these markers of opioidergic tone might help predict success in certain types of weight management programs.
PMCID: PMC4125886  PMID: 24291355
naltrexone; hedonic eating; food addiction; cortisol; nausea; obesity
8.  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 
Psychoneuroendocrinology  2013;38(12):10.1016/j.psyneuen.2013.07.016.
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 781 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.
PMCID: PMC3844074  PMID: 23969421
financial strain; cortisol; positive affect; negative affect
9.  Soda and Cell Aging: Associations between Sugar-Sweetened Beverage Consumption and Leukocyte Telomere Length in Healthy Adults from the National Health and Nutrition Examination Surveys 
American journal of public health  2014;104(12):2425-2431.
We tested whether leukocyte telomere length maintenance, which underlies healthy cellular aging, provides a link between sugar-sweetened beverage (SSB) consumption and risk of cardiometabolic disease. We examined cross-sectional associations between consumption of SSBs, diet soda and fruit juice and telomere length in a nationally representative sample of healthy adults.
The study population included 5,309 adults, aged 20 to 65 years, with no prior history of diabetes or cardiovascular disease, from the 1999–2002 National Health and Nutrition Examination Surveys. Leukocyte telomere length was assayed from DNA specimens. Diet was assessed using 24-hour dietary recalls. Associations were examined using multivariate linear regression for the outcome of log-transformed telomere length.
After adjustment for sociodemographic and health-related characteristics, sugar-sweetened soda consumption was associated with shorter telomeres (β=−0.010, 95% CI −0.020, −0.001, P=0.04). Consumption of 100% fruit juice was marginally associated with longer telomeres (β= 0.016, 95% CI −0.000, 0.033). No significant associations were observed between consumption of diet sodas or non-carbonated sugar-sweetened beverages and telomere length.
Regular consumption of sugar-sweetened sodas may influence metabolic disease development through accelerated cell aging.
PMCID: PMC4229419  PMID: 25322305
10.  Childhood Socioeconomic Status, Telomere Length, and Susceptibility to Upper Respiratory Infection 
Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood.
At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+CD28− T-lymphocyte telomere length (in a subset, n = 135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over 5 post-exposure days.
Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+CD28− telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+CD28− cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.
PMCID: PMC3795973  PMID: 23845919
11.  Longer leukocyte telomere length in Costa Rica's Nicoyan Peninsula: A population-based study 
Experimental gerontology  2013;48(11):10.1016/j.exger.2013.08.005.
Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, p<0.05) than in other areas of Costa Rica, providing evidence of a biological pathway to which this notable longevity may be related. This relationship remains unchanged (79 base pairs, p<0.05) after statistically controlling for nineteen potential biological, dietary and social and demographic mediators. Thus the difference in mean leukocyte telomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages.
PMCID: PMC3819141  PMID: 23988653
telomere length; Costa Rica; aging; biomarkers; socioeconomic; longevity
12.  Clues to Maintaining Calorie Restriction? Psychosocial Profiles of Successful Long-term Restrictors 
Appetite  2014;79:106-112.
To combat the obesity epidemic, interventions and treatment often recommend low-calorie dieting. Calorie restriction (CR) as a weight intervention, however, is often unsuccessful, as most people cannot sustain the behavior. Yet one small group has maintained extreme CR over years—members of the CR Society and followers of The CR Way. This study examined stable psychosocial characteristics of these individuals to identify traits that may promote success at long-term CR. In 65 participants, we measured diet, eating behaviors, and personality traits comparing calorie restrictors to two age-, gender-, ethnicity-, and education-matched comparison groups (normal weight and overweight/obese). We first tested whether the CR group restricted calories without indications of eating disorder pathology, and second, what crystallized psychosocial characteristics set them apart from their non-restricting comparisons. Results indicated the CR group averaged 10 years of CR but scored lower than comparison groups on measures of disordered eating (p < .001) and psychopathology (p < .001). Particularly against overweight/obese participants, CR participants scored lower on neuroticism (p < .04) and hostility (p < .01), and were stronger in future time orientation (p< .05). Overall, CR profiles reflected high self-control and well being, except for having few close relationships. This study suggests a potential predisposition for successful long-term CR without disordered eating. Since modifying trait factors may be unrealistic, there may be psychosocial boundaries to the capacity for sustaining CR. Paralleling a movement towards personalized medicine, this study points toward a personalized behavioral medicine model in behavioral nutrition and treatment of overweight/obesity.
PMCID: PMC4198019  PMID: 24747211
dieting; calorie restriction; obesity; personality; time perspective; eating disorders
13.  Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity 
Psychoneuroendocrinology  2013;38(9):1698-1708.
Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.
PMCID: PMC4028159  PMID: 23490070
Oxidative stress; biological aging; chronic stress; acute stress; DNA/RNA damage; cortisol; hypothalamic-pituitary-adrenal axis; eustress; resilience; reactive oxygen species
14.  Stress and Telomere Biology: A Lifespan Perspective 
Psychoneuroendocrinology  2013;38(9):1835-1842.
In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes ver the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.
PMCID: PMC3735679  PMID: 23639252
Telomere length; telomerase; stress; lifespan; prenatal; fetal/developmental programming; childhood stress; mental health; depression; lifestyle
15.  Gender differences in the prospective associations of self-reported sleep quality with biomarkers of systemic inflammation and coagulation: findings from the Heart and Soul Study 
Journal of psychiatric research  2013;47(9):10.1016/j.jpsychires.2013.05.004.
Systemic inflammation is proposed as a putative mechanism underlying the link between poor sleep and cardiovascular disease. The aim of present study was to investigate the cross-sectional and prospective associations of self-reported sleep quality with biomarkers of inflammation and coagulation implicated in coronary heart disease (CHD) and to explore whether these associations differed between men and women. To this end, measures of sleep quality and markers of inflammation, including circulating levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (CRP), and fibrinogen were assessed at baseline in 980 participants with established CHD and 626 at 5-year follow-up. In the sample as a whole, subjective sleep quality was unrelated to inflammatory markers in cross-sectional and prospective analyses. However, in gender stratified analyses, adjusting for age, ethnicity, education, body mass index, and regular snoring, poorer subjective sleep quality at baseline was prospectively associated with 5-year increases in IL-6 (b= 0.14, SE= 0.05, p= 0.003), CRP (b= 0.21, SE= 0.09, p= 0.02), and fibrinogen (b= 18.02, SE= 7.62, p= 0.02) in women but not men. These associations remained independent of lifestyle/psychosocial factors, medical comorbidities, medication use, and cardiac function. Women who reported baseline sleep disturbances characterized by a tendency to wake up too early in the morning also showed significant 5-year increases in circulating IL-6 that withstood covariate adjustment. Further research is necessary to elucidate the pathways that underlie gender-specific associations between subjective sleep quality and markers of inflammation and coagulation as this may help clarify gender disparities in CHD.
PMCID: PMC3864775  PMID: 23746737
sleep; inflammation; gender; coronary heart disease
16.  Seasonal variation of peripheral blood leukocyte telomere length in Costa Rica: a population based observational study 
Peripheral blood leukocyte telomere length is increasingly being used as a biomarker of aging, but its natural variation in human populations is not well understood. Several other biomarkers show seasonal variation, as do several determinants of leukocyte telomere length. We examined whether there was monthly variation in leukocyte telomere length in Costa Rica, a country with strong seasonal differences in precipitation and infection.
We examined a longitudinal population based cohort of 581 Costa Rican adults age 60 and above, from which blood samples were drawn between October 2006 and July 2008. Leukocyte telomere length was assayed from these samples using the quantitative PCR method. Multivariate regression models were used to examine correlations between month of blood draw and leukocyte telomere length.
Telomere length from peripheral blood leukocytes varied by as much as 200 base pairs depending on month of blood draw, and this difference is not likely to be due to random variation. A moderate proportion of this association is statistically accounted for by month and region specific average rainfall. We found shorter telomere length associated with greater rainfall.
There are two possible explanations of our findings. First, there could be relatively rapid month-to-month changes in leukocyte telomere length. This conclusion would have implications for understanding the natural population dynamics of telomere length. Second, there could be seasonal differences in constituent cell populations. This conclusion would suggest that future studies of leukocyte telomere length use methods to account for the potential impact of constituent cell type.
PMCID: PMC4136920  PMID: 24615938
telomere length; seasonality; lymphocytes; infection; rainfall
17.  Chronic Stress Increases Vulnerability to Diet-Related Abdominal Fat, Oxidative Stress, and Metabolic Risk 
Psychoneuroendocrinology  2014;46:14-22.
In preclinical studies, the combination of chronic stress and a high sugar/fat diet is a more potent driver of visceral adiposity than diet alone, a process mediated by peripheral Neuropeptide Y (NPY).
In a human model of chronic stress, we investigated whether the synergistic combination of highly palatable foods (HPF; high sugar/fat) and stress was associated with elevated metabolic risk. Using a case-control design, we compared 33 post-menopausal caregivers (the chronic stress group) to 28 age-matched low-stress control women on reported HPF consumption (modified Block Food Frequency Questionnaire), waistline circumference, truncal fat ultrasound, and insulin sensitivity using a three-hour oral glucose tolerance test. A fasting blood draw was assayed for plasma NPY and oxidative stress markers (8-hydroxyguanosine and F2-Isoprostanes).
Among chronically stressed women only, greater HPF consumption was associated with greater abdominal adiposity, oxidative stress, and insulin resistance at baseline (all p’s ≤.01). Furthermore, plasma NPY was significantly elevated in chronically stressed women (p<.01), and the association of HPF with abdominal adiposity was stronger among women with high versus low NPY. There were no significant predictions of change over one-year, likely due to high stability (little change) in the primary outcomes over this period.
Chronic stress is associated with enhanced vulnerability to diet-related metabolic risk (abdominal adiposity, insulin resistance, and oxidative stress). Stress-induced peripheral NPY may play a mechanistic role.
PMCID: PMC4104274  PMID: 24882154
Psychological stress; obesity; abdominal adiposity; metabolic syndrome; pre-diabetes
18.  The Reward-Based Eating Drive Scale: A Self-Report Index of Reward-Based Eating 
PLoS ONE  2014;9(6):e101350.
Why are some individuals more vulnerable to persistent weight gain and obesity than are others? Some obese individuals report factors that drive overeating, including lack of control, lack of satiation, and preoccupation with food, which may stem from reward-related neural circuitry. These are normative and common symptoms and not the sole focus of any existing measures. Many eating scales capture these common behaviors, but are confounded with aspects of dysregulated eating such as binge eating or emotional overeating. Across five studies, we developed items that capture this reward-based eating drive (RED). Study 1 developed the items in lean to obese individuals (n = 327) and examined changes in weight over eight years. In Study 2, the scale was further developed and expert raters evaluated the set of items. Study 3 tested psychometric properties of the final 9 items in 400 participants. Study 4 examined psychometric properties and race invariance (n = 80 women). Study 5 examined psychometric properties and age/gender invariance (n = 381). Results showed that RED scores correlated with BMI and predicted earlier onset of obesity, greater weight fluctuations, and greater overall weight gain over eight years. Expert ratings of RED scale items indicated that the items reflected characteristics of reward-based eating. The RED scale evidenced high internal consistency and invariance across demographic factors. The RED scale, designed to tap vulnerability to reward-based eating behavior, appears to be a useful brief tool for identifying those at higher risk of weight gain over time. Given the heterogeneity of obesity, unique brief profiling of the reward-based aspect of obesity using a self-report instrument such as the RED scale may be critical for customizing effective treatments in the general population.
PMCID: PMC4076308  PMID: 24979216
19.  Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity 
Psychophysiology  2013;51(3):257-266.
What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3 we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or ‘stress signatures’—how our body and mind react to stress both in the moment and over the longer term—are linked to how complexly we speak under stress.
PMCID: PMC4059522  PMID: 24354732
cognitive complexity; cognition; stress reactivity; cortisol reactivity; language
20.  Is the Belief in Meritocracy Palliative for Members of Low Status Groups? Evidence for a Benefit for Self-Esteem and Physical Health via Perceived Control 
Consensually held ideologies may serve as the cultural “glue” that justifies hierarchical status differences in society (e.g. Augustinos, 1998). Yet to be effective these beliefs need to be embraced by low-status groups. Why would members of low-status groups endorse beliefs that justify their relative disadvantage? We propose that members of low-status groups in the United States may benefit from some system-justifying beliefs (such as the belief in meritocracy) to the extent that these beliefs emphasize the perception of control over future outcomes. In 2 studies, among women, lower-SES women, and women of color, we found a positive relationship between the belief in meritocracy and well-being (self-esteem and physical health) that was mediated by perceived control. Members of low-status groups may benefit from some system-justifying beliefs to the extent that these beliefs, like the belief in meritocracy, emphasize the perception of control over future outcomes.
PMCID: PMC3769703  PMID: 24039310
System Justification; Meritocracy; Self-Esteem; Socio-economic Status
21.  Food insecurity with past experience of restrained eating is a recipe for increased gestational weight gain 
Appetite  2013;65:178-184.
Food insecurity is linked to higher weight gain in pregnancy, as is dietary restraint. We hypothesized that pregnant women exposed to marginal food insecurity, and who reported dietary restraint before pregnancy, will paradoxically show the greatest weight gain. Weight outcomes were defined as total kilograms, observed-to-recommended weight gain ratio, and categorized as adequate, inadequate or excessive weight gain based on 2009 Institute of Medicine guidelines. A likelihood ratio test assessed the interaction between marginal food insecurity and dietary restraint and found significant. Adjusted multivariate regression and multinomial logistic models were used to estimate weight gain outcomes. In adjusted models stratified by dietary restraint, marginal insecurity and low restraint was significantly associated with lower weight gain and weight gain ratio compared to food secure and low restraint. Conversely, marginal insecurity and high restraint was significantly associated with higher weight gain and weight gain ratio compared to food secure and high restraint. Marginal insecurity with high restraint was significantly associated with excessive weight gain. Models were consistent when restricted to low-income women and full-term deliveries. In the presence of marginal food insecurity, women who struggle with weight and dieting issues may be at risk for excessive weight gain.
PMCID: PMC3800106  PMID: 23402720
food insecurity; dietary restraint; weight gain; dieting; disordered eating; pregnancy
22.  Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999–2002 
The purpose of this study was to examine the association between socioeconomic status (SES) and leukocyte telomere length (LTL) – a marker of cell aging that has been linked to stressful life circumstances – in a nationally representative, socioeconomically and ethnically diverse sample of US adults aged 20–84. Using data from the National Health and Nutrition Examination Survey (NHANES), 1999–2002, we found that respondents who completed less than a high school education had significantly shorter telomeres than those who graduated from college. Income was not associated with LTL. African-Americans had significantly longer telomeres than whites, but there were no significant racial/ethnic differences in the association between education and telomere length. Finally, we found that the association between education and LTL was partially mediated by smoking and body mass index but not by drinking or sedentary behavior.
PMCID: PMC3666871  PMID: 23540359
socioeconomic status; cell aging; telomere length; health behavior; United States
23.  Relation between Leukocyte Telomere Length and Incident Coronary Heart Disease Events (From the 1995 Canadian Nova Scotia Health Survey) 
The American journal of cardiology  2013;111(7):962-967.
Leukocyte telomere length has been proposed as a biomarker of cellular aging and atherosclerosis. We sought to determine whether leukocyte telomere length is independently associated with incident coronary heart disease (CHD) in the general population. Telomere length was measured using a polymerase chain reaction method for participants enrolled in the 1995 Nova Scotia Health Survey (n=1,917). The primary endpoint was first occurrence of fatal and non-fatal CHD events. During a mean follow-up of 8.7 years, 164 fatal or non-fatal CHD events occurred. Compared to participants in the longest tertile of telomere length, those in the middle and shortest tertiles had increased incidence of CHD events (6.2, 11.2 and 12.2 per 1000 person-years, respectively). After adjustment for demographics, traditional risk factors and inflammatory markers including hs-CRP, IL-6, and sICAM-1, those in the middle tertile had significantly elevated risk for incident CHD (hazard ratio [HR] 1.63, 95% CI 1.07–2.51, p=0.02) compared to the longest tertile, whereas the risk for those in the shortest tertile was non-significantly elevated (HR 1.25, 95% CI 0.82–1.90, p=0.30). In conclusion, these findings do not support a linear association between leukocyte telomere length and incident CHD risk in the general population.
PMCID: PMC3602395  PMID: 23375186
coronary heart disease; telomere; risk prediction
24.  Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial 
Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind 4-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5 g/day n-3 PUFAs, (2) l.25 g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. identifier: NCT00385723
PMCID: PMC3545053  PMID: 23010452
omega-3; omega-6; telomeres; inflammation; cell aging; nutritional neuroscience; oxidative stress; F2-isoprostanes; fish oil
25.  Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length 
In adults, one of the major determinants of leukocyte telomere length (LTL), a predictor of age-related diseases and mortality, is cumulative psychosocial stress exposure. More recently we reported that exposure to maternal psychosocial stress during intrauterine life is associated with LTL in young adulthood. The objective of the present study was to determine how early in life this effect of stress on LTL is apparent by quantifying the association of maternal psychosocial stress during pregnancy with newborn telomere length.
Study Design
In a prospective study of N = 27 mother-newborn dyads maternal pregnancy-specific stress was assessed in early gestation and cord blood peripheral blood mononuclear cells were subsequently collected and analyzed for LTL measurement.
After accounting for the effects of potential determinants of newborn LTL (gestational age at birth, weight, sex, and exposure to antepartum obstetric complications), there was a significant, independent, linear effect of pregnancy-specific stress on newborn LTL that accounted for 25% of the variance in adjusted LTL (β = −0.099; P = .04).
Our finding provides the first preliminary evidence in human beings that maternal psychological stress during pregnancy may exert a “programming” effect on the developing telomere biology system that is already apparent at birth, as reflected by the setting of newborn LTL.
PMCID: PMC3612534  PMID: 23200710
fetal/developmental programming of health and disease risk; maternal psychosocial stress; newborn telomere biology

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