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Background: Although vaccines are largely effective and safe, there is variability in post-vaccination experience regarding antibody response, side effects, and affective outcomes. Vaccine mindsets, specific beliefs about the vaccine, may be associated with post-vaccination experience. This is important since mindsets are malleable and may help decrease vaccine hesitancy and improve post-vaccination experience. Methods: In a prospective study, we measured overall positive vaccine mindset and specific mindsets regarding efficacy, body response, and side effects. We tested whether vaccine mindsets before vaccination predicted neutralizing antibody response, side effects, vaccine-related stress, and affective outcomes (general stress, sadness, and happiness). Antibody response was assessed one month and six months after participants completed a SARS-CoV-2 vaccination series. Side effect experience and affective reactions were assessed daily on the vaccination day and the subsequent five days. Results: There was no significant association between the aggregate vaccine mindset score and neutralizing antibody response; however, people with a more positive vaccine mindset reported fewer side effects, less same-day vaccine-related anxiety, and improved affective outcomes after vaccination. In secondary analyses, when specific mindsets were explored, the mindset that vaccine side effects are a sign of treatment efficacy predicted higher antibodies, but not side effects experience and vaccine-related anxiety. Vaccine efficacy and body-response mindsets predicted fewer side effects, vaccine-related anxiety, and improved affective outcomes after vaccination. Conclusion: These findings underscore the potential of vaccine mindsets in enhancing the overall post-vaccination experience and, in some cases, increasing antibody response.

BackgroundGiven its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators.MethodsPlasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes.ResultsThe retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat.ConclusionThese preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Abstract Telomere length (TL) is a marker of biological aging, and shorter telomeres have been associated with several medical and psychiatric disorders, including cardiometabolic dysregulation and Major Depressive Disorder (MDD). In addition, studies have shown shorter TL to be associated with poorer response to certain psychotropic medications, and our previous work suggested shorter TL and higher telomerase activity (TA) predicts poorer response to Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Using a new group of unmedicated medically healthy individuals with MDD (n = 48), we sought to replicate our prior findings demonstrating that peripheral blood mononuclear cell (PBMC) TL and TA predict response to SSRI treatment and to identify associations between TL and TA with biological stress mediators and cardiometabolic risk indices. Our results demonstrate that longer pre-treatment TL was associated with better response to SSRI treatment (β = .407 p = .007). Additionally, we observed that TL had a negative relationship with allostatic load (β = − .320 p = .017) and a cardiometabolic risk score (β = − .300 p = .025). Our results suggest that PBMC TL reflects, in part, the cumulative effects of physiological stress and cardiovascular risk in MDD and may be a biomarker for predicting SSRI response.

Abstract As concerns related to the COVID-19 pandemic continue, it is critical to understand the impact of vaccination type on neutralizing antibody response durability as well as to identify individual difference factors related to decline in neutralization. This was a head-to-head comparison study following 498 healthy, community volunteers who received the BNT162b2 (n = 287), mRNA-1273 (n = 149), and Ad26.COV2.S (n = 62). Participants completed questionnaires and underwent blood draws prior to vaccination, 1 month, and 6 months after the vaccination series, and neutralizing antibody (nAB) titers at 1- and 6-months post vaccination were quantified using a high-throughput pseudovirus assay. Over 6 months of follow-up, nABs declined in recipients of BNT162b2 and mRNA-1273, while nABs in recipients of Ad26.COV2.S showed a significant increase. At the 6-month time point, nABs to Ad26.COV2.S were significantly higher than nABs to BNT162b2 and equivalent to mRNA-1273. Irrespective of follow-up timing, being older was associated with lower nAB for participants who received BNT162b2 and Ad26.COV2.S but not for those who received mRNA-1273. A higher baseline BMI was associated with a lower nAB for Ad26.COV2.S recipients but not for recipients of other vaccines. Women and non-smokers showed higher nAB compared to men and current smokers, respectively. The durability of neutralizing antibody responses differed by vaccine type and several sociodemographic factors that predicted response. These findings may inform booster recommendations in the future.

A meta-analysis of 17 cohorts of mitochondrial disease patients reveals that OxPhos defects are associated with signs of hypermetabolism. Experiments in patient-derived fibroblast show that mitochondrial OxPhos defects trigger hypermetabolism in a cell-autonomous manner and this is linked to accelerated telomere shortening and epigenetic aging.

Abstract Early detection of diseases such as COVID-19 could be a critical tool in reducing disease transmission by helping individuals recognize when they should self-isolate, seek testing, and obtain early medical intervention. Consumer wearable devices that continuously measure physiological metrics hold promise as tools for early illness detection. We gathered daily questionnaire data and physiological data using a consumer wearable (Oura Ring) from 63,153 participants, of whom 704 self-reported possible COVID-19 disease. We selected 73 of these 704 participants with reliable confirmation of COVID-19 by PCR testing and high-quality physiological data for algorithm training to identify onset of COVID-19 using machine learning classification. The algorithm identified COVID-19 an average of 2.75 days before participants sought diagnostic testing with a sensitivity of 82% and specificity of 63%. The receiving operating characteristic (ROC) area under the curve (AUC) was 0.819 (95% CI [0.809, 0.830]). Including continuous temperature yielded an AUC 4.9% higher than without this feature. For further validation, we obtained SARS CoV-2 antibody in a subset of participants and identified 10 additional participants who self-reported COVID-19 disease with antibody confirmation. The algorithm had an overall ROC AUC of 0.819 (95% CI [0.809, 0.830]), with a sensitivity of 90% and specificity of 80% in these additional participants. Finally, we observed substantial variation in accuracy based on age and biological sex. Findings highlight the importance of including temperature assessment, using continuous physiological features for alignment, and including diverse populations in algorithm development to optimize accuracy in COVID-19 detection from wearables.

Mindfulness meditation may improve well-being at work; however, effects on food cravings and metabolic health are not well known. We tested effects of digital meditation, alone or in combination with a healthy eating program, on perceived stress, cravings, and adiposity. We randomized 161 participants with overweight and moderate stress to digital meditation (‘MED,’ n = 38), digital meditation + healthy eating (‘MED+HE,’ n = 40), active control (‘HE,’ n = 41), or waitlist control (‘WL,’ n = 42) for 8 weeks. Participants (n = 145; M(SD) BMI: 30.8 (5.4) kg/m2) completed baseline and 8-week measures of stress (Perceived Stress Scale), cravings (Food Acceptance and Awareness Questionnaire) and adiposity (sagittal diameter and BMI). ANCOVAs revealed that those randomized to MED or MED+HE (vs. HE or WL) showed decreases in perceived stress (F = 15.19, p < .001, η2 = .10) and sagittal diameter (F = 4.59, p = .03, η2 = .04), with no differences in cravings or BMI. Those high in binge eating who received MED or MED+HE showed decreases in sagittal diameter (p = .03). Those with greater adherence to MED or MED+HE had greater reductions in stress, cravings, and adiposity (ps < .05). A brief digital mindfulness-based program is a low-cost method for reducing perceptions of stress and improving abdominal fat distribution patterns among adults with overweight and moderate stress. Future work should seek to clarify mechanisms by which such interventions contribute to improvements in health. Trial registration: Clinical trial registrationhttp://www.ClinicalTrials.gov: identifier NCT03945214.

Abstract Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.

Abstract Early childhood and pregnancy are two sensitive periods of heightened immune plasticity, when exposure to adversity may disproportionately increase health risks. However, we need deeper phenotyping to disentangle the impact of adversity during sensitive periods from that across the total lifespan. This study examined whether retrospective reports of adversity during childhood or pregnancy were associated with inflammatory imbalance, in an ethnically diverse cohort of 53 low-income women seeking family-based trauma treatment following exposure to interpersonal violence. Structured interviews assessed early life adversity (trauma exposure ≤ age 5), pregnancy adversity, and total lifetime adversity. Blood serum was assayed for pro-inflammatory (TNF-a, IL-1ß, IL-6, and CRP) and anti-inflammatory (IL-1RA, IL-4, and IL-10) cytokines. CD14+ monocytes were isolated in a subsample (n = 42) and gene expression assayed by RNA sequencing (Illumina HiSeq 4000; TruSeq cDNA library). The primary outcome was a macrophage-associated M1/M2 gene expression phenotype. To evaluate sensitivity and specificity, we contrasted M1/M2 gene expression with a second, clinically-validated macrophage-associated immunosuppressive phenotype (endotoxin tolerance) and with pro-inflammatory and anti-inflammatory cytokine levels. Adjusting for demographics, socioeconomic status, and psychopathology, higher adversity in early life (ß = .337, p = 0.029) and pregnancy (ß = .332, p = 0.032) were each associated with higher M1/M2 gene expression, whereas higher lifetime adversity (ß = −.341, p = 0.031) was associated with lower immunosuppressive gene expression. Adversity during sensitive periods was uniquely associated with M1/M2 imbalance, among low-income women with interpersonal violence exposure. Given that M1/M2 imbalance is found in sepsis, severe COVID-19 and myriad chronic diseases, these findings implicate novel immune mechanisms underlying the impact of adversity on health.

The prevalence of overweight and obesity is greatest amongst Black women in the U.S., contributing to disproportionately higher type 2 diabetes prevalence compared to White women. Insulin resistance, independent of body mass index, tends to be greater in Black compared to White women, yet the mechanisms to explain these differences are not completely understood. The gut microbiome is implicated in the pathophysiology of obesity, insulin resistance and cardiometabolic disease. Only two studies have examined race differences in Black and White women, however none characterizing the gut microbiome based on insulin sensitivity by race and sex. Our objective was to determine if gut microbiome profiles differ between Black and White women and if so, determine if these race differences persisted when accounting for insulin sensitivity status. In a pilot cross-sectional analysis, we measured the relative abundance of bacteria in fecal samples collected from a subset of 168 Black (n = 94) and White (n = 74) women of the National Growth and Health Study (NGHS). We conducted analyses by self-identified race and by race plus insulin sensitivity status (e.g. insulin sensitive versus insulin resistant as determined by HOMA-IR). A greater proportion of Black women were classified as IR (50%) compared to White women (30%). Alpha diversity did not differ by race nor by race and insulin sensitivity status. Beta diversity at the family level was significantly different by race (p = 0.033) and by the combination of race plus insulin sensitivity (p = 0.038). Black women, regardless of insulin sensitivity, had a greater relative abundance of the phylum Actinobacteria (p = 0.003), compared to White women. There was an interaction between race and insulin sensitivity for Verrucomicrobia (p = 0.008), where among those with insulin resistance, Black women had four fold higher abundance than White women. At the family level, we observed significant interactions between race and insulin sensitivity for Lachnospiraceae (p = 0.007) and Clostridiales Family XIII (p = 0.01). Our findings suggest that the gut microbiome, particularly lower beta diversity and greater Actinobacteria, one of the most abundant species, may play an important role in driving cardiometabolic health disparities of Black women, indicating an influence of social and environmental factors on the gut microbiome.

This meta-analysis examined the association between the level of childhood psychosocial stressors and telomere length, an important health biomarker. The meta-analysis, including 27 samples and 16,238 participants, found a significant association of −0.08 between a higher level of childhood stressors and shorter telomere length at a mean age of 42 across studies. Moderator analyses showed a trend in the direction of effect sizes being significantly larger with shorter times between the stressors and telomere measurement. Moderator analyses showed significantly higher effect sizes for studies that used a categorical method for assessing child stressor level and for assays completed with qPCR rather than with the Southern blot method. There was no significant moderation of effect size by whether study assayed leukocytes or buccal cells, whether the study assessed child stressor level by memory-based recall versus archival records, and whether the study controlled for age, sex, or additional variables. The results, focused on childhood events, add to prior findings that perceived stress and negative emotions are associated with telomere length.

A diversity of scales capture facets of reward-related eating (RRE). These scales assess food cravings, uncontrolled eating, addictive behavior, restrained eating, binge eating, and other eating behaviors. However, these scales differ in terms of the severity of RRE they capture. We sought to incorporate the items from existing scales to broaden the 9-item Reward-based Eating Drive scale (RED-9; Epel et al., 2014), which assesses three dimensions of RRE (lack of satiety, preoccupation with food, and lack of control over eating), in order to more comprehensively assess the entire spectrum of RRE. In a series of 4 studies, we used Item Response Theory models to consider candidate items to broaden the RED-9. Studies 1 and 2 evaluated the abilities of additional items from existing scales to increase the RED-9’s coverage across the spectrum of RRE. Study 3 evaluated candidate items identified in Studies 1 and 2 in a new sample to assess the extent to which they accounted for more variance in areas less well-covered by the RED-9. Study 4 tested the ability of the RED-13 to provide consistent coverage across the range of the RRE spectrum. The resultant RED-13 accounted for greater variability than the RED-9 by reducing gaps in coverage of RRE in middle-to-low ranges. Like the RED-9, the RED-13 was positively correlated with BMI. The RED-13 was also positively related to a diagnosis of type 2 diabetes as well as cravings for sweet and savory foods. In summary, the RED-13 is a brief self-report measure that broadly captures the spectrum of RRE and may be a useful tool for identifying individuals at risk for overweight or obesity.

Background. Accumulating evidence supports leukocyte telomere length (LTL) as a biological marker of cellular aging. Poor sleep is a risk factor for age-related disease; however, the extent to which sleep accounts for variation in LTL is unknown. Methods. The present study examined associations of self-reported sleep duration, onset latency, and subjective quality with LTL in a community-dwelling sample of 245 healthy women in midlife (aged 49–66 years). Results. While sleep duration and onset latency were unrelated to LTL, women reporting poorer sleep quality displayed shorter LTL (r=0.14, P=0.03), independent of age, BMI, race, and income (b=55.48, SE=27.43, P=0.04). When analyses were restricted to participants for whom sleep patterns were chronic, poorer sleep quality predicted shorter LTL independent of covariates and perceived psychological stress. Conclusions. This study provides the first evidence that poor sleep quality explains significant variation in LTL, a marker of cellular aging.

Rationale : Chronic stress has been related to lower telomerase, an enzyme that helps preserve the integrity of DNA and slow immunological aging. However, it is unknown whether daily psychological processes reflecting healthy emotion regulation protect against stress-related immune-aging. Methods : We examined basal telomerase activity in a sample of 72 healthy premenopausal women across a range of stress levels, including 35 mothers caring for a child with autism and 37 low-stress control mothers of healthy children. Participants completed a nightly diary over the course of a week, reporting their exposure to positive and negative events. Then they rated the extent to which they employed various emotion-regulation strategies in response to these events. Within-subject weekly means for all measures were calculated. In addition, composite scores for positive affect in response to positive daily events and negative affect in response to daily stressors were calculated, and weekly means obtained. Depressive symptoms were assessed using the Inventory of Depressive Symptoms. On day 4 of the study week, a fasting blood draw was performed to measure peripheral blood mononuclear cells (PBMC) telomerase activity. Results : Higher telomerase activity was significantly associated with the use of more resilient emotion regulation strategies, including more positive emotional responses to positive daily events (r=0.27, p=0.02) and increased savoring of positive daily events (r=0.24, p=0.04). In general, negative emotional responses and rumination in response to daily stressors were not related to telomerase with two exceptions: lower telomerase was associated with greater emotional suppression (r= − 0.34, p

Telomere length (TL) is an important marker of cellular aging that can be examined from birth to death and provide information about health status and disease risk. TL shortens in early childhood with the majority of the shortening occurring by age 4. TL is associated with stress and obesity in adults. It is possible that exposure to early life stressors and excess adiposity from birth and the first year of life may impact the rate of telomere shortening. Few studies have examined TL in the first years of life, and none of them have examined stress and obesity in infants.We examined TL by qPCR using genomic DNA from dried blood spots in a sample of 109 four-year-old, low-income Latino children and their mothers. TL is expressed as T/S (the ratio of telomeric product vs. single copy gene product). This group of children and their mothers were recruited prenatally in San Francisco at which time socio-demographic and health history was assessed. In addition, child weight and length and maternal body mass index (BMI) have been assessed annually from birth with the child's weight and length measured also at birth and 6 months of age. Maternal depressive symptoms were assessed prenatally, at 4–6 weeks postpartum and annually throughout the follow-up period. Child behavior was evaluated using the child behavior checklist (CBCL) at 3 and 4 years of age for internalizing and externalizing behaviors. Student's t-tests were performed to compare TL in relationship to different childhood exposures – maternal depression, child overweight and obesity, and socio-demographic factors such as child sex, ethnicity, and socioeconomic status. Factors that were significant at p

Oxidative stress (an imbalance between free radicals and the ability to neutralize them with antioxidants) occurs in several mental illnesses, including major depression (MDD). A major antioxidant in humans is glutathione peroxidase, which reduces GSSH to GSH, increasing glutathione's ability to scavenge free radicals. The brain, and the hippocampus (HC) in particular, is particularly sensitive to oxidative stress, and HC oxidative stress (particularly in the CA1 and CA3 & dentate gyrus [CA3&DG] subfields) may contribute to major depression.Nineteen medication-free subjects with MDD and 19 matched controls underwent 4T MRI scanning of the HC and had fasting morning venipuncture for peripheral oxidative stress assessment. Two of the MDD subjects did not have glutathione (GSH) and/or glutathione (GSSG) data. Because of the preliminary nature of the study, no corrections for multiple comparisons were applied.Across all subjects, the antioxidant Vitamin C was directly correlated with total HC (p

Rationale/statement of the problem : Major depressive disorder (MDD) and other serious mental illnesses are associated with high rates of comorbid medical illnesses. Many of these comorbid conditions are more typically seen in the aged, raising the possibility that these psychiatric illnesses are associated with accelerated aging. An emerging biomarker of cell aging and of increased risk of medical illness is leukocyte telomere length, and several studies have now characterized leukocyte telomere length in MDD and other psychiatric illnesses. Fewer psychiatric studies have characterized the activity of telomerase, an enzyme that can elongate and preserve telomeric DNA, or have investigated the biochemical mediators of accelerated telomere shortening. Methods : Seven studies examining telomere length in MDD, three studies in schizophrenia, two studies in bipolar illness, two studies in PTSD, and one study in generalized anxiety disorder were reviewed, as were one study of telomerase activity in MDD and one study in schizophrenia. Additional studies in chronically stressed individuals and in individuals with histories of childhood adversity were also reviewed. Results : Shortened leukocyte telomeres have been demonstrated in MDD, bipolar illness, schizophrenia, anxiety disorders, and post-traumatic stress disorder, although in some studies, only subgroups of patients (e.g., those with longer lifetime exposure to the illness, those with poor responses to treatment, or those with preexisting histories of childhood adversity) showed shortened telomeres. Leukocyte telomere shortening is correlated with peripheral indices of increased oxidative stress and increased immune activation. Two studies (one in caregivers with high depression ratings and one in unmedicated patients with MDD) reported elevated peripheral blood mononuclear cell (PBMC) telomerase activity, perhaps representing a compensatory attempt by the body to preserve endangered telomeres. Preliminary data in MDD suggest that relatively low telomerase activity before treatment, and greater treatment-associated increases in telomerase activity, are associated with better antidepressant responses. This, plus the preliminary observation that PBMC telomerase activity is directly correlated with hippocampal volume (by MRI) in MDD, support emerging preclinical data that telomerase has intrinsic neurotrophic and antidepressant effects. Conclusion : Telomere shortening in MDD and certain other psychiatric conditions may, at least partially, reflect chronic exposure to inflammation and oxidation. As such, it may be a bellwether of increased medical risk, or it may play a more direct causal role in accelerated aging. The interplay of telomere integrity and telomerase activity may be an important determinant of psychiatric and medical outcome. Overall, the data are consistent with the view that MDD and certain other psychiatric illnesses have systemic manifestations beyond the brain and call into question the dichotomy of “mental” vs. “physical” illnesses.

Obesity and the metabolic syndrome (MetS) predispose to multiple diseases and to accelerated cell aging as indexed by accelerated shortening of telomeres in peripheral blood mononuclear cells (PBMC's). Major depressive disorder (MDD) is often associated with MetS and is also associated with increased disease risk and PBMC telomere shortening. A potential role of leptin in telomere shortening has been suggested, but prior results have been inconsistent and no study has yet assessed this relationship in MDD. The goal of this study was to assess the relationship between serum leptin concentrations and PBMC telomere length in MDD and in controls and to assess whether this relationship is mediated by body-mass index (BMI) or the homeostatic model assessment of insulin resistance (HOMA-IR), two principal components of the MetS.Eighteen medication-free MDD subjects (11 female, 7 male, mean age 37.1 + 2.7 years) and 17 healthy controls (11 female, 6 male, mean age 37.8 + 3.0 years) had blood drawn for assay of fasting morning levels of leptin, glucose, and insulin and PBMC telomere length. The groups did not differ on BMI (24.66 + 3.72 vs. 24.77 + 4.29, respectively, n.s.). Analyses were co-varied for age and sex, with and without BMI.In the combined group, serum leptin concentrations were inversely correlated with telomere length (r= − 0.33, p0.30, and t=1.49, p>0.10, respectively), but leptin concentrations remained significantly correlated with telomere length (t= − 2.88, p=0.007).Relatively high leptin concentrations, in the presence or absence of increased BMI and insulin resistance, may be a risk factor for telomere shortening. While this was demonstrated here in individuals with MDD, a similar relationship in non-depressed individuals cannot be ruled out because of the small sample size.

Rationale/statement of the problem : Leukocyte telomere length (LTL), a marker of cellular aging, has been proposed as a pathogenic mechanism by which depression may confer increased risk of adverse cardiovascular events. Prior studies have suggested that depression and depressive symptoms are associated with shorter LTL, but these studies are limited by small sample sizes, selective enrollment of participants (e.g. psychiatric outpatients), and lack of adjustment for cardiovascular risk factors and other covariates. The present study examines the association of LTL with depression and depressive symptoms in a large, populations-based cohort. Methods : Participants included 2225 apparently healthy individuals from the 1995 Nova Scotia Health Survey (NSHS95) population-based study. Depressive symptoms were assessed by the Center for Epidemiological Studies-Depression (CES-D) scale. LTL was assessed by a real-time polymerase chain reaction method. Linear regression analyses were used to examine the association between LTL and depressive symptoms, probable depressive disorder (CES-D ≥ 10 or CES-D ≥ 16), and specific depressive symptom clusters (depressed affect, somatic concerns, positive affect, and interpersonal problems). These analyses were adjusted for clinical and demographic factors thought to potentially confound the association between depression and LTL, including: age, sex, body mass index, Framingham risk score, and previous ischemic heart disease. Results : In an unadjusted model, each 1-point increase on the CES-D was significantly associated with a 3.49 base pair increase in LTL (95% CI = 0.39-6.60, p = 0.03). However, this association was not significant after adjustment for age and sex (B=1.20, 95% CI = − 1.85-4.25, p = 0.44) and further adjustment for other covariates (all p's ≥ 0.37). Neither probable depressive disorder nor specific depressive symptom clusters were independently associated with LTL after adjustment for covariates. Conclusion : Concurrent depressive symptoms were not independently associated with LTL in a large population-based study. These results suggest that the excess risk of cardiovascular disease risk associated with concurrent depression may not be due to accelerated cellular aging.

Rationale/statement of the problem : Substantial evidence suggests conditions in intrauterine life may play a critical role in subsequent health and disease susceptibility related outcomes (i.e., the concept of fetal or developmental programming of health and disease). The elucidation of biological mechanisms underlying these effects is an area of active investigation. We suggest that telomere biology may represent a novel mechanism underlying the effects of a disparate set of suboptimal intrauterine exposures on various health and disease risk phenotypes. From an evolutionary-developmental perspective, energy substrate availability (i.e., nutrition) and challenges that have the potential to impact the structural or functional integrity and survival of the organism (i.e., stress) likely represent the most important environmental considerations underlying natural selection and developmental plasticity. Maternal stress and nutrition in pregnancy therefore represent attractive candidate processes in the context of fetal programming of telomere biology. Our previous work has established an important role for prenatal stress and stress-related processes in adult telomere biology Methods : In two longitudinal birth cohorts, stress- and nutrition-related processes were assessed during pregnancy and telomere length (TL) was subsequently measured in newborns (cord blood) and infants (buccal cells). Results : (1) Among the nutrition-related factors, maternal lower folate levels (an essential methyl donor) and higher triglyceride concentrations in early pregnancy were significantly and independently associated with shorter newborn TL. (2) Among psychosocial stress-related measures, higher maternal pregnancy-specific stress was associated with shorter newborn TL. (3) Maternal estrogen (E3) levels during early pregnancy were associated with longer infant TL. Conclusion : Taken together, our findings provide the first evidence in humans that maternal nutrition and stress-related processes during pregnancy may exert a programming effect on the newborn and infant telomere biology system. In utero telomere biology represents a potential molecular mechanism whereby different exposures in this critical developmental period before birth could impact subsequent health and disease susceptibility related outcomes over the life span, including aging and longevity

Prior studies of Hypothalamic-Pituatary-Adrenal (HPA) associations with hippocampal (HC) volume have yielded inconsistent results. This might be due to the use of basal cortisol rather than cortisol reactivity measures and to the use of cortisol in isolation from related steroids. Therefore, in this study, we assessed the relationship of HC volume to cortisol awakening responses (CARs) and to the ratio of cortisol/DHEA in depressed (MDD) subjects and healthy controls. We additionally assessed cortisol correlations with individual HC subfield volumes.A 4 Tesla T1 MR imaging was conducted for HC volume for 19 MDD subjects and 19 matched controls. Fasting morning serum was assayed for cortisol and DHEA. In addition, salivary samples were assayed for cortisol for 17 MDDs and 15 controls across 3 days: at Waking (Sample 1) and at +30 minutes after waking (Sample 2). The CAR is the difference between daily Sample 1 and Sample 2 salivary concentrations. The slope of the CARincrease was obtained by dividing the CAR by the actual length of time between the two sample collections. Serum cortisol was not significantly correlated with HC volume. However, in the MDD group, serum DHEA, a putative anti-glucocorticoid, was positively correlated with HC volume (p

Chronic psychological stress increases inflammation, providing a mechanism for the elevated risk of infectious, autoimmune and cardiovascular diseases in chronically stressed persons. While the HPA axis plays an important role in mediating the link between stressful events and inflammatory processes, it is becoming increasingly clear that immune cells can become resistant to cortisol, resulting in diminished regulation of inflammation. One potential mechanism of cortisol resistance results from decreased glucocorticoid receptor (GR) expression in immune cells during elevated cortisol exposure. Chronic stress results in chronic high cortisol exposure leading to decreased immune cell GR expression that in turn is associated with greater immune activation. Using flow cytometry we measured immune activation and GR expression (geometric mean fluorescence intensity [gMFI]) in 10 immune cell subsets in 25 post-menopausal females (10 caregivers [CGs] and 15 controls [CNTLs]). Mann–Whitney and Pearson correlations were employed for statistical analysis with p

The cellular enzyme elomerase replenishes telomeric DNA, which can be lost during repeated mitoses or during exposure to inflammation and oxidation. However, telomerase may have other, non-canonical functions, including (in animal models) antidepressant and neurogenesis-enhancing effects. In this study, we determined the relationship between telomerase activity [(measured in peripheral blood mononuclear cells (PBMCs)] and hippocampal (HC) volume in depressed individuals (MDDs) and matched controls.Nineteen medication-free subjects with MDD and 17 matched healthy controls underwent 4T MRI scanning and fasting morning venipuncture for assessment of unstimulated PBMC telomerase activity. Due to the exploratory nature of the study, corrections for multiple comparisons were not applied.Hippocampal volume was smaller, but not significantly so, in the MDDs than the controls. As reported previously, MDD subjects had significantly higher PBMC telomerase activity than the controls (p=0.007). Within the MDD group (but not in the control group or in the combined sample), PBMC telomerase activity was positively correlated with HC volume (r=0.49, p