Geroscience: linking aging to chronic disease.

Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches. Given that the elderly population is dramatically increasing and that aging is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, it is critical to expand geroscience research directed at extending human healthspan.

COVID-19 Vaccine Side Effects and Long-Term Neutralizing Antibody Response : A Prospective Cohort Study.

BACKGROUND: Concern about side effects is a common reason for SARS-CoV-2 vaccine hesitancy. OBJECTIVE: To determine whether short-term side effects of SARS-CoV-2 messenger RNA (mRNA) vaccination are associated with subsequent neutralizing antibody (nAB) response. DESIGN: Prospective cohort study. SETTING: San Francisco Bay Area. PARTICIPANTS: Adults who had not been vaccinated against or exposed to SARS-CoV-2, who then received 2 doses of either BNT162b2 or mRNA-1273. MEASUREMENTS: Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose. RESULTS: 363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years [SD, 11.9]), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years [SD, 5.3]). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later. LIMITATIONS: The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown. CONCLUSION: Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake. PRIMARY FUNDING SOURCE: National Institute on Aging.

New Directions in Geroscience: Integrating Social and Behavioral Drivers of Biological Aging.

ABSTRACT: The "geroscience hypothesis" posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. Although geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome-the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity.

Did a workplace sugar-sweetened beverage sales ban reduce anxiety-related sugar-sweetened beverage consumption during the COVID-19 pandemic?

OBJECTIVE: Workplace sugar-sweetened beverage (SSB) sales bans can reduce SSB consumption. Because stress and anxiety can promote sugar consumption, we examined whether anxiety among hospital employees during the COVID-19 pandemic was associated with changes in SSB consumption and explored whether this relationship varied by exposure to a workplace SSB sales ban. DESIGN: In a prospective, controlled trial of workplace SSB sales bans, we examined self-reported anxiety (generalised anxiety disorder-7) and self-reported SSB consumption (fluid ounces/d) before (July 2019) and during (May 2020) the COVID-19 pandemic. SETTING: Hospital sites in two conditions (four with SSB sales bans and three without sales bans) in Northern California. PARTICIPANTS: We sampled 580 participants (hospital employees) from a larger trial of sales bans; all were regular consumers of SSB (minimum 3/week at main trial enrollment). This subsample was chosen based on having appropriately timed data for our study questions. RESULTS: Across conditions, participants reduced SSB consumption over the study period. However, participants with higher pandemic-era anxiety scores experienced smaller reductions in SSB consumption after 9 months compared with those with lower anxiety scores (ß = 0·65, P < 0·05). When the sample was disaggregated by sales ban condition, this relationship held for participants in the control group (access to SSB at work, ß = 0·82, P < 0·05), but not for those exposed to an SSB sales ban (ß = 0·42, P = 0·25). CONCLUSIONS: SSB sales bans likely reduce SSB consumption through multiple pathways; buffering stress-related consumption may be one mechanism.

Food insecurity, poor diet, and metabolic measures: The roles of stress and cortisol.

Food insecurity is highly prevalent and linked to poorer diet and worse metabolic outcomes. Food insecurity can be stressful, and could elicit chronic psychological and physiological stress. In this study, we tested whether stress could be used to identify those at highest risk for worse diet and metabolic measures from food insecurity. Specifically, we hypothesized that cortisol (a physiological marker of stress) and perceived psychological stress would amplify the link between food insecurity and hyperpalatable food intake as well as metabolic measures. In a sample of 624 Black and White women aged 36-43 who participated in the NHLBI Growth and Health Study's midlife assessment, we assessed associations between food insecurity with hyperpalatable food intake (high fat + high sodium foods; high fat + high sugar foods; and high carbohydrate + high sodium foods), and metabolic measures (fasting glucose, insulin resistance, and waist circumference). We found that food insecurity was associated with higher levels of perceived stress (R2 = 0.09), and greater intake of high fat + high sugar (hyperpalatable) foods (R2 = 0.03). In those with higher cumulative cortisol (as indexed by hair cortisol), food insecurity was associated with higher levels of fasting glucose. Neither cortisol nor perceived stress moderated any other relationships, and neither variable functioned as a mediator in sensitivity analyses. Given these largely null findings, further research is needed to understand the role stress plays in the chronic health burdens of food insecurity.

A Lens on Caregiver Stress in Cancer: Longitudinal Investigation of Cancer-Related Stress and Telomere Length Among Family Caregivers of Adult Patients With Cancer.

OBJECTIVE: Family members are typically the primary caregivers of patients with chronic illnesses. Family caregivers of adult relatives with cancer are a fast-growing population, yet the physical consequences of their stress due to the cancer in the family have been poorly understood. This study examined the bidirectional relations of the perceived stress of family caregivers of individuals recently diagnosed with cancer and leukocyte cellular aging indexed by telomere length for 2 years. METHODS: Family caregivers ( N = 168; mean age = 51 years, 70% female, 46% Hispanic, 36% spouse to the patient) of patients with colorectal cancer provided psychological data and peripheral blood samples approximately 4 (T1), 12 (T2), and 21 months (T3) after diagnosis. Time-lagged cross-panel modeling was used to test the associations of perceived cancer-related stress and telomere length, controlling for age, sex, and body mass index. RESULTS: Cancer-related stress was highest at T1 and decreased by 1 year. Greater cancer-related stress predicted longer telomere length at subsequent assessments for 2 years ( ß ≥ 0.911, p ≤ .019). However, telomere length did not change significantly for 2 years overall and did not prospectively predict cancer-related stress over this period. CONCLUSIONS: Findings suggest the need to better understand how the perceived stress of colorectal cancer caregivers, which tends to be intense for a relatively short period compared with dementia caregiving, may impact immune cell distributions and telomere length. These findings emphasize the need for further knowledge about psychobiological mechanisms of how cancer caregiving may impact cellular aging.

Acute and Chronic Stress Associations With Blood Pressure: An Ecological Momentary Assessment Study on an App-Based Platform.

OBJECTIVE: This study examined the within- and between-person associations of acute and chronic stress with blood pressure (BP) and heart rate (HR) using an app-based research platform. METHODS: We examined data from 31,964 adults (aged 18-90 years) in an app-based ecological momentary assessment study that used a research-validated optic sensor to measure BP. RESULTS: Within-person associations revealed that moments with (versus without) acute stress exposure were associated with higher systolic (SBP; b = 1.54) and diastolic BP (DBP; b = 0.79) and HR ( b = 1.53; p values < .001). During moments with acute stress exposure, higher acute stress severity than usual was associated with higher SBP ( b = 0.26), DBP ( b = 0.09), and HR ( b = 0.40; p values < .05). During moments without acute stress, higher background stress severity than usual was associated with higher BP and HR (SBP: b = 0.87, DBP: b = 0.51, HR: b = 0.69; p values < .001). Between-person associations showed that individuals with more frequent reports of acute stress exposure or higher chronic stress severity had higher SBP, DBP, and HR ( p values < .05). Between-person chronic stress severity moderated within-person physiological responses to stress such that individuals with higher chronic stress severity had higher average BP and HR levels but showed smaller responses to momentary stress. CONCLUSIONS: Technological advancements with optic sensors allow for large-scale physiological data collection, which provides a better understanding of how stressors of different timescales and severity contribute to momentary BP and HR in daily life.

Early life adversity predicts an accelerated cellular aging phenotype through early timing of puberty.

BACKGROUND: The current study examined if early adversity was associated with accelerated biological aging, and if effects were mediated by the timing of puberty. METHODS: In early mid-life, 187 Black and 198 White (Mage = 39.4, s.d.age = 1.2) women reported on early abuse and age at first menstruation (menarche). Women provided saliva and blood to assess epigenetic aging, telomere length, and C-reactive protein. Using structural equation modeling, we created a latent variable of biological aging using epigenetic aging, telomere length, and C-reactive protein as indicators, and a latent variable of early abuse using indicators of abuse/threat events before age 13, physical abuse, and sexual abuse. We estimated the indirect effects of early abuse and of race on accelerated aging through age at menarche. Race was used as a proxy for adversity in the form of systemic racism. RESULTS: There was an indirect effect of early adversity on accelerated aging through age at menarche (b = 0.19, 95% CI 0.03-0.44), in that women who experienced more adversity were younger at menarche, which was associated with greater accelerated aging. There was also an indirect effect of race on accelerated aging through age at menarche (b = 0.25, 95% CI 0.04-0.52), in that Black women were younger at menarche, which led to greater accelerated aging. CONCLUSIONS: Early abuse and being Black in the USA may both induce a phenotype of accelerated aging. Early adversity may begin to accelerate aging during childhood, in the form of early pubertal timing.

Intergenerational effects of maternal lifetime stressor exposure on offspring telomere length in Black and White women.

BACKGROUND: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers. METHOD: Mothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted. RESULTS: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers. CONCLUSIONS: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.

Psychological stress is associated with arterial inflammation in people living with treated HIV infection.

Stress and depression are increasingly recognized as cerebrovascular risk factors, including among high stress populations such as people living with HIV infection (PLWH). Stress may contribute to stroke risk through activation of neural inflammatory pathways. In this cross-sectional study, we examined the relationships between stress, systemic and arterial inflammation, and metabolic activity in stress-related brain regions on 18F-fluorodeoxyglucose (FDG)-PET in PLWH. Participants were recruited from a parent trial evaluating the impact of alirocumab on radiologic markers of cardiovascular risk in people with treated HIV infection. We administered a stress battery to assess different forms of psychological stress, specifying the Perceived Stress Scale as the primary stress measure, and quantified plasma markers of inflammation and immune activation. Participants underwent FDG-PET of the brain, neck, and chest. Age- and sex-matched control participants without HIV infection were selected for brain FDG-PET comparisons. Among PLWH, we used nonparametric pairwise correlations, partial correlations, and linear regression to investigate the association between stress and 1) systemic inflammation; 2) atherosclerotic inflammation on FDG-PET; and metabolic activity in 3) brain regions in which glucose metabolism differed significantly by HIV serostatus; and 4) in a priori defined stress-responsive regions of interest (ROI) and stress-related neural network activity (i.e., ratio of amygdala to ventromedial prefrontal cortex or temporal lobe activity). We studied 37 PLWH (mean age 60 years, 97% men) and 29 control participants without HIV (mean age 62 years, 97% men). Among PLWH, stress was significantly correlated with systemic inflammation (r = 0.33, p = 0.041) and arterial inflammation in the carotid (r = 0.41, p = 0.023) independent of age, race/ethnicity, traditional vascular risk factors and health-related behaviors. In voxel-wise analyses, metabolic activity in a cluster corresponding to the anterior medial temporal lobes, including the bilateral amygdalae, was significantly lower in PLWH compared with controls. However, we did not find a significant positive relationship between stress and this cluster of decreased metabolic activity in PLWH, a priori defined stress-responsive ROI, or stress-related neural network activity. In conclusion, psychological stress was associated with systemic and carotid arterial inflammation in this group of PLWH with treated infection. These data provide preliminary evidence for a link between psychological stress, inflammation, and atherosclerosis as potential drivers of excess cerebrovascular risk among PLWH.

Controlled trial of a workplace sales ban on sugar-sweetened beverages.

OBJECTIVE: To examine the effectiveness of a workplace sugar-sweetened beverage (SSB) sales ban on reducing SSB consumption in employees, including those with cardiometabolic disease risk factors. DESIGN: A controlled trial of ethnically diverse, full-time employees who consumed SSB heavily (sales ban n 315; control n 342). Outcomes included standardised measures of change in SSB consumption in the workplace (primary) and at home between baseline and 6 months post-sales ban. SETTING: Sutter Health, a large non-profit healthcare delivery system in Northern California. PARTICIPANTS: Full-time employees at Sutter Health screened for heavy SSB consumption. RESULTS: Participants were 66·1 % non-White. On average, participants consumed 34·7 ounces (about 1 litre) of SSB per d, and the majority had an elevated baseline BMI (mean = 29·5). In adjusted regression analyses, those exposed to a workplace SSB sales ban for 6 months consumed 2·7 (95 % CI -4·9, -0·5) fewer ounces of SSB per d while at work, and 4·3 (95 % CI -8·4, -0·2) fewer total ounces per d, compared to controls. Sales ban participants with an elevated BMI or waist circumference had greater post-intervention reductions in workplace SSB consumption. CONCLUSIONS: Workplace sales bans can reduce SSB consumption in ethnically diverse employee populations, including those at higher risk for cardiometabolic disease.

Parental sensitivity modifies the associations between maternal prenatal stress exposure, autonomic nervous system functioning and infant temperament in a diverse, low-income sample.

Evidence suggests that adversity experienced during fetal development may shape infant physiologic functioning and temperament. Parental sensitivity is associated with child stress regulation and may act as a buffer against risk for intergenerational health effects of pre- or postnatal adversity. Building upon prior evidence in a racially and ethnically diverse sample of infants (M infant age = 6.5 months) and women of low socioeconomic status, this study examined whether coded parenting sensitivity moderated the association between an objective measure of prenatal stress exposures (Stressful Life Events (SLE)) and infant parasympathetic (respiratory sinus arrhythmia; RSA) or sympathetic (pre-ejection period; PEP) nervous system functioning assessed during administration of the Still-Face-Paradigm (SFP) (n = 66), as well as maternal report of temperament (n = 154). Results showed that parental sensitivity moderated the associations between prenatal stress exposures and infant RSA reactivity, RSA recovery, PEP recovery, and temperamental negativity. Findings indicate that greater parental sensitivity is associated with lower infant autonomic nervous system reactivity and greater recovery from challenge. Results support the hypothesis that parental sensitivity buffers infants from the risk of prenatal stress exposure associations with offspring cross-system physiologic reactivity and regulation, potentially shaping trajectories of health and development and promoting resilience.

Effects of Early Life Adversity on Pubertal Timing and Tempo in Black and White Girls: The National Growth and Health Study.

OBJECTIVE: Although exposure to abuse in early life predicts earlier pubertal timing, especially for girls, it is unclear if this association generalizes to nonabuse stressors. In addition, the impact of race on the stress-maturation association remains unknown. To address these issues, we examined whether race moderates the effects of early adversity on pubertal timing and tempo using a longitudinal study design. METHODS: In a cohort of 9- and 10-year-old Black and White girls, pubertal (areolar and pubic hair) maturation was assessed annually for 7 years. In adulthood, 368 participants (186 Black, 182 White) reported on abuse and nonabuse stressors they experienced from ages 0 to 12 years. RESULTS: Early life abuse was associated with earlier pubertal timing, as indexed by younger age at menarche (b = -0.22, p = .005, 95% confidence interval [CI] = -0.39 to -0.06) and greater pubic hair development (b = 0.11, p = .003, 95% CI = 0.04 to 0.18), in addition to slower pubertal tempo, as indexed by slower rate of pubic hair (b = -0.03, p < .001, 95% CI = -0.05 to -0.01) and areolar (b = -0.02, p = .02, 95% CI = -0.03 to -0.003) development. These associations were not found for nonabuse adversity. Black girls with early life abuse had greater pubic hair development (b = 0.23, p < .001, 95% CI = 0.12 to 0.35) and were slower in pubic hair tempo (b = -0.07, p < .001, 95% CI = -0.09 to -0.04) than their White counterparts. CONCLUSIONS: Screening for early life abuse may help address health disparities related to earlier pubertal timing.

Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults.

Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.

Childhood stress and midlife depression in women: the influence of diet quality.

OBJECTIVE: How does diet quality (DQ) moderate associations between serious childhood stress exposures and adult depression? METHODS: We analyzed a cohort of Californian women at midlife (N=382; age 36-42). Serious childhood stress was defined as high perceived stress during childhood or adverse childhood experiences (ACEs) of physical abuse, sexual abuse, and/or household substance abuse. Women were dichotomized by current depression risk (high/low). The Healthy Eating Index (HEI)-2015 and Alternate Healthy Eating Index (AHEI)-2010 measured current DQ from 3-day food records. Interactions between childhood stress exposures and DQ indices were tested one-by-one in multivariable Poisson regression models. RESULTS: Depression risks associated with endorsing all 3 ACEs differed by HEI and AHEI scores, as did risks associated with endorsing high perceived stress, physical abuse, and sexual abuse by AHEI. Where DQ moderated stress-depression associations, predicted prevalences of high depression risk did not vary with DQ among women endorsing the particular childhood stressors. However, among non-endorsing women, predicted high depression risk prevalences were significantly lower with higher DQ compared to in their stress-exposed counterparts - e.g. at the 90th AHEI percentile, depression prevalences were ∼20% among 'non-childhood-stressed' women versus 48.8% (high perceived stress, sexual abuse), 52.0% (physical abuse), and 73.0% (3 ACEs) in 'childhood-stressed' women. CONCLUSIONS: Higher current DQ, particularly as aligned with chronic disease prevention guidelines, predicts lower depression risk in women with low childhood adversity. DQ did not buffer depression risk in women with high childhood stress. Further research is warranted to examine persistent pathways of depression risk and diet's role within.

Psychological Resources and Biomarkers of Health in the Context of Chronic Parenting Stress.

BACKGROUND: Epidemiological studies link psychological resources to better physical health. One reason may be that psychological resources are protective in stressful contexts. This study tested whether indeed psychological resources are protective against biological degradation for healthy mid-life women under the chronic stress of caring for a child with an autism spectrum disorder diagnosis ("caregivers"). METHODS: We tested whether five types of psychosocial resources (i.e., eudaimonic well-being, autonomy, purpose in life, self-acceptance, and mastery) were associated with biological indices of aging in a sample of mid-life women stratified by chronic stress; half were caregivers (n = 92) and half were mothers of neurotypical children (n = 91; controls). Selected stress and age related biological outcomes were insulin resistance (HOMA-IR), systemic inflammation (IL-6, CRP), and cellular aging (leukocyte telomere length). We tested whether each resource was associated with these biomarkers, and whether caregiving status and high parenting stress moderated that relationship. RESULTS: All the psychological resources except mastery were significantly negatively associated with insulin resistance, while none were related to systemic inflammation or telomere length. The relationships between eudaimonic well-being and HOMA-IR, and self-acceptance and HOMA-IR, were moderated by parental stress; lower resources were associated with higher insulin resistance, but only for women reporting high parental stress. The well-known predictors of age and BMI accounted for 46% of variance in insulin resistance, and psychological resources accounted for an additional 13% of variance.  CONCLUSION: These findings suggest that higher eudaimonic well-being and greater self-acceptance may be protective for the metabolic health of mid-life women, and particularly in the context of high parenting stress. This has important implications given the rising rates of both parental stress and metabolic disease, and because psychological interventions can increase eudaimonic well-being and self-acceptance.

Transactions between Maternal and Child Depressive Symptoms Emerge Early in Life.

Maternal depression is a robust risk factor for children's internalizing symptoms; however, the intergenerational transmission of mood disorders is likely more complex than unidirectional parent-directed effects. Theoretical models support transactional associations between maternal and child symptomatology over time but have not been well examined, especially in younger high-risk samples. The present investigation examined predictive transactional relations between maternal depression and children's internalizing in toddlerhood and early childhood using a cross-lagged panel model. Participants were 162 low-income, largely racial/ethnic minority mothers and their offspring (32% African American, 16% White, 52% Other/Multiethnic; 53% female) who were assessed when children were 18 months and 4 years old. There were significant cross-sectional relations between maternal depressive and child internalizing symptoms when children were 18 months but not 4 years of age. Cross-lagged associations were evident such that maternal depression symptoms at 18 months were positively associated with internalizing symptoms among children at 4 years, adjusting for prior maternal symptom levels and the cross-sectional correlations between maternal-child symptoms at 18 months. Within the same model, children's internalizing symptoms at 18 months were also positively associated with maternal depressive symptoms at 4 years, adjusting for prior child symptom levels and cross-sectional correlations. This study is among the first to demonstrate that transactional relations between maternal and child mood symptoms occur as early as toddlerhood/early childhood. Findings highlight the potential utility of inclusive, family-focused interventions that support both parents and children in the treatment of early emotional problems.

Enhanced Stress Resilience Training in Surgeons: Iterative Adaptation and Biopsychosocial Effects in 2 Small Randomized Trials.

OBJECTIVE: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers. SUMMARY OF BACKGROUND AND DATA: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown. METHODS: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity"). RESULTS: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls. CONCLUSIONS: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

Exploratory Analysis of Racial/Ethnic and Educational Differences in a Randomized Controlled Trial of a Mindfulness-Based Weight Loss Intervention.

OBJECTIVE: People of color and lower socioeconomic groups have higher obesity prevalence, lose less weight compared with Whites and higher socioeconomic groups, and are underrepresented in randomized controlled trials of mindfulness-based interventions. We examined whether mindfulness approaches reduce disparities in weight loss interventions. METHODS: We analyzed data from a randomized controlled trial of 194 participants with obesity (41% participants of color, 36% without college degree) comparing a 5.5-month mindfulness-based weight loss intervention to an active-control with identical diet-exercise guidelines. We assessed attendance, 18-month attrition, and weight change at 6, 12, and 18 months by race/ethnicity and education level using linear mixed models, adjusting for baseline body mass index, age, and education or race/ethnicity, respectively. RESULTS: Participants without versus with a college degree attended fewer sessions and had higher attrition across interventions. Participants of color attended fewer intervention sessions in the mindfulness compared with the control intervention. Overall, participants of color lost significantly less weight at 12 and 18 months compared with Whites. However, during the 6- to 18-month maintenance period, we found an interaction of intervention arm, race/ethnicity, and time (p = .035), indicating that participants of color compared with Whites regained more weight in the control (0.33 kg/mo; p = .005) but not mindfulness intervention (0.06 kg/mo; p = .62). Participants without a college degree had greater initial weight loss in the mindfulness compared to control intervention from 0 to 6 months (-0.46 kg/mo; p = .039). CONCLUSIONS: Although disparities persist, mindfulness approaches may mitigate some racial/ethnic and socioeconomic differences in weight loss compared with conventional diet-exercise programs.Trial Registration: Clinicaltrials.gov registration: NCT00960414.

Pre-treatment allostatic load and metabolic dysregulation predict SSRI response in major depressive disorder: a preliminary report.

BACKGROUND: Major depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepressant-treatment outcomes. METHODS: We determined pre-treatment AL and MetD in 67 healthy controls and 34 unmedicated, medically healthy MDD subjects. Following this, MDD subjects completed 8-weeks of open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and were categorized as 'Responders' (⩾50% improvement in depression severity ratings) or 'Non-responders' (<50% improvement). Logistic and linear regressions were performed to determine if pre-treatment AL or MetD scores predicted SSRI-response. Secondary analyses examined cross-sectional differences between MDD and control groups. RESULTS: Pre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) (p = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder (p = 0.022 and 0.040, respectively), such that higher pre-treatment AL and MetD were associated with poorer SSRI-treatment outcomes. Pre-treatment AL and MetD of Responders were similar to Controls, while those of Non-responders were significantly higher than both Responders (p = 0.025 and 0.033, respectively) and Controls (p = 0.039 and 0.001, respectively). CONCLUSIONS: These preliminary findings suggest that indices of metabolic and hypothalamic-pituitary-adrenal-axis dysregulation are associated with poorer SSRI-treatment response. To our knowledge, this is the first study to demonstrate that these markers of medical disease risk also predict poorer antidepressant outcomes.