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1.  Genetic and Environmental Effects on Diurnal Dehydroepiandrosterone Sulfate Concentrations in Middle-Aged Men 
Psychoneuroendocrinology  2011;36(10):1441-1452.
Summary
Background
Dehydroepiandrosterone sulfate (DHEAS) is important for its association with immune system function and health outcomes. The characterization of the genetic and environmental contributions to daily DHEAS concentrations is thus important for understanding the genetics of health and aging.
Methods
Saliva was collected from 783 middle-aged men (389 complete pairs and 5 unpaired twins) as part of the Vietnam Era Twin Study of Aging. Samples were taken at multiple specified time points across two non-consecutive days in the home and one day at the study sites. A twin modeling approach was used to estimate genetic and environmental contributions for time-specific and average DHEAS concentrations.
Results
There was a consistent diurnal pattern for DHEAS concentrations in both at-home and day-of-testing (DOT) measures, which was highest at awakening and decreased slightly throughout the day. Heritability estimates were significant for measures at 10am, 3pm and bedtime for the in-home days and at 10am and 3pm on the DOT, ranging between 0.37 and 0.46.
Conclusions
The significant heritability estimates later in the day reflect time-specific genetic effects for DHEAS, compared with prior twin and family designs studies which frequently used averaged morning-only measures. Additive genetic influences on DHEAS concentrations were consistent between at-home and DOT measures.
doi:10.1016/j.psyneuen.2011.03.018
PMCID: PMC3183407  PMID: 21570195
DHEAS; diurnal concentrations; genetics; twin study; aging; men
2.  Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study 
Psychoneuroendocrinology  2011;37(7):917-928.
Summary
Background
Psychological distress and metabolic dysregulation are associated with markers of accelerated cellular aging, including reduced telomerase activity and shortened telomere length. We examined whether participation in a mindfulness-based intervention, and, secondarily, improvements in psychological distress, eating behavior, and metabolic factors are associated with increases in telomerase activity in peripheral blood mononuclear cells (PBMCs).
Methods
We enrolled 47 overweight/obese women in a randomized waitlist-controlled pilot trial (n = 47) of a mindfulness-based intervention for stress eating and examined changes in telomerase activity from pre- to post-intervention. In secondary analyses, changes in telomerase activity across the sample were examined in relation to pre- to post-intervention changes in psychological distress, eating behavior, and metabolic factors (weight, serum cortisol, fasting glucose and insulin, and insulin resistance).
Results
Both groups increased in mean telomerase activity over 4 months in intent-to-treat and treatment efficacy analyses (p < 0.001). Nonsignificant trends showed that greater attendance was associated with increases in telomerase, and telomerase increases were 18% higher among ‘as treated’ participants compared to controls. Across groups, changes in chronic stress, anxiety, dietary restraint, dietary fat intake, cortisol, and glucose were negatively correlated with changes in telomerase activity. In exploratory analyses, decreases in dietary fat intake partially mediated the association between dietary restraint and telomerase activity with marginal significance.
Conclusions
While there was no clear effect of the intervention on telomerase activity, there was a striking pattern of correlations between improvements in psychological distress, eating behavior, and metabolic health and increases in telomerase activity. These findings suggest that telomerase activity may be in part regulated by levels of both psychological and metabolic stress.
doi:10.1016/j.psyneuen.2011.10.008
PMCID: PMC3384690  PMID: 22169588
Stress; Anxiety; Mindfulness; Dietary restraint; Telomerase; Cell aging; Cortisol
3.  Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study 
Journal of Obesity  2011;2011:651936.
Psychological distress and elevated cortisol secretion promote abdominal fat, a feature of the Metabolic Syndrome. Effects of stress reduction interventions on abdominal fat are unknown. Forty-seven overweight/obese women (mean BMI = 31.2) were randomly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating. We assessed mindfulness, psychological distress, eating behavior, weight, cortisol awakening response (CAR), and abdominal fat (by dual-energy X-ray absorptiometry) pre- and posttreatment. Treatment participants improved in mindfulness, anxiety, and external-based eating compared to control participants. Groups did not differ on average CAR, weight, or abdominal fat over time. However, obese treatment participants showed significant reductions in CAR and maintained body weight, while obese control participants had stable CAR and gained weight. Improvements in mindfulness, chronic stress, and CAR were associated with reductions in abdominal fat. This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR, which may reduce abdominal fat over time.
doi:10.1155/2011/651936
PMCID: PMC3184496  PMID: 21977314
6.  Acute and chronic stress increase DHEAS concentrations in rhesus monkeys 
Psychoneuroendocrinology  2010;35(7):1055-1062.
Summary
Most studies on the stress-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis have focused on glucocorticoids, while few studies have investigated the adrenal secretion of dehydroepiandrosterone-sulfate (DHEAS), which is unique to primates. Monkeys were chair-restrained for two hours per day for seven consecutive days, and blood samples were collected upon placement in the chair, and at 15, 30, 60 and 120 minutes later. Like cortisol, DHEAS concentrations increased throughout the initial session of chair restraint (acute stress). Unlike the cortisol response, which decreased after repeated exposure to the stressor, the DHEAS response was sustained throughout the seventh session of restraint (chronic stress) and response to the seventh session of restraint did not differ from the DHEAS response to the initial session. Like cortisol, DHEAS concentrations showed a diurnal rhythm with higher concentrations in the morning compared to the evening and a decrease in response to dexamethasone (DEX) administration. After repeated exposure to the stressor, the suppression of DHEAS in response to dexamethasone was more complete, suggesting an increase in negative feedback sensitivity. These data show that DHEAS concentrations increase in response to both acute and chronic (repeated) stress and provide another measure of HPA activity that parallels cortisol during acute responses to stress but diverges in chronic or repeated stress.
doi:10.1016/j.psyneuen.2010.01.006
PMCID: PMC2894999  PMID: 20153584
hypothalamic-pituitary-adrenal (HPA) axis; dehydroepiandrosterone sulfate; DHEAS; cortisol; stress; rhesus monkey; dexamethasone
7.  Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony 
PLoS Pathogens  2011;7(7):e1002155.
Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.
Author Summary
Infection from adenoviruses, viruses that cause a variety of illnesses in humans, monkeys, and other animals, has conventionally been thought to be species-specific. We used the Virochip, a microarray designed to detect all viruses, to identify a new species of adenovirus (TMAdV, or titi monkey adenovirus) that caused a deadly outbreak in a colony of New World titi monkeys at the California National Primate Research Center (CNPRC), and also infected a human researcher. One-third of the monkeys developed pneumonia and liver inflammation, and 19 of 23 monkeys died or were humanely euthanized. The unusually high death rate (83%) makes titi monkeys unlikely to be natural hosts for TMAdV, and the genomic sequence of TMAdV revealed that it is very different from any other known adenovirus. The researcher developed an acute respiratory illness at the onset of the outbreak, and was found to be infected by TMAdV by subsequent antibody testing. A clinically ill family member with no prior contact with the CNPRC also tested positive. Further investigation is needed to identify whether TMAdV originated from humans, monkeys, or another animal. The discovery of TMAdV suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.
doi:10.1371/journal.ppat.1002155
PMCID: PMC3136464  PMID: 21779173
8.  Neurobiological and Neuropsychiatric Effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS) 
DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.
doi:10.1016/j.yfrne.2008.11.002
PMCID: PMC2725024  PMID: 19063914
Dehydroepiandrosterone; DHEA; DHEAS; neuroprotection; neurogenesis; apoptosis; depression; schizophrenia; dementia; cortisol

Results 1-8 (8)